; $4.245: “Ln‘l' "r v 'H" gmi‘uzf‘ . 41'» ’{IW «$3315, a ‘95» 29 .914.“ ... "254$ :f'rI 4“? ’I15 '? . "3" _ W" m‘I' ’1: :1' o'I ..-I."‘;,'! "1" q: ,L.4‘!'{£14r14:"1111‘{ I‘ . I. “'4’; ENE“! . 1 ‘ 1' . ..J‘d< 'lt’ . .310! 14 “c j"’ “ , I ‘I I... V~h|1L II 0|.l.“ I 7“, 1h" 15" fig: 4%}: $473214 IIIquuIZIfi???‘ ’L‘h‘lf’:nlw "" “‘19 1. 1 . 'J V ‘ I J .45 _. .>' .‘... I'vr .VI“ - 4.1P‘3’z“£_1"}_:£"3‘~ H 4.. “‘1, $1. (.3.- 1, ‘4/1‘31m4' 6:," Fix .110. J ”Y, ° . Ml; 0‘" “24": I ,1. ’Z‘l'cL‘4k f1. . .- ' J‘ “Y 3.13%“ gut." :3 J h . t -‘ ' t 5.1: mt“ . 19;“..9944- a " “" .J!U-:'.:‘,".':f ‘11; ' ”01)“... '.‘I71W‘,tl-.-nf-. 4... K1»... 1 4“ l 1.1.11 ' H“ Q18.“ "1‘43" .H‘Iflfiq‘ofiq 3 "W "I {L3 4.3:“; 0"": I. 3‘ 'x - I If; 4 .s l J'.,‘{ L't " \‘ (I'D. P}‘°3 {353. 45.1”)va .‘n‘nu. ”a. . . "39$ 5“ 1:17.?" U. ("'4’ '5’ ,o'. “3;qu O? "J’ ' '4 v 1.5":- :' “2"." {£97379 "£1.10: “I J. "' .“W I .A., " . 4'01...” 1V?" ‘ '9‘... ‘. , l‘. . 2“/,”X:‘: 'Q‘iiwil'fi'fis‘tflg.’”.1255‘? 4.31:,” far: ‘45“); .:| ‘3')“ {(‘IIJ'DI‘PF ‘f‘f‘h ?;W3 ,I! ‘ .1)?"~l4‘ '. ”n ' . ',l'l'- ‘- ." v. '.‘ "'n‘\" " o 5.. o. .1..:.’~ 4:114. ”an”? ”.‘.;~‘.‘:..!' 3. ,m. 1954‘. 1m, HUI"? WU? .9 ‘Miiaw “9 ?-"'3‘;*~~7.""a"rf~‘ HI“: 45:41:53,. L ‘-‘1'..f'v'«v '1 ‘ "1' M 3" 5".“177} 't L ' "J. :[J'gfi - I44“); 73?." Vie. {419}; .“157.'~41\«},sz££941.’1.~1:511”? '.-‘-f: 513 99:19:11.. ,.1-;x§§’-"4;"5:12:41‘5fllfgil‘5374‘194r".-52‘Q-Isggl;gcxr"';:~4 “‘ " ~, 4 g? o. "' .1' .“‘ .". if! I- 'H ." . " . " "I..- . ‘4"?‘4" 3“?“ '7 W ' ..'- : 5'15” . “'f - 0': H" '4 .. 2 tall] 1.!..}1r.‘5£,“¢j,1-.~k, .1 "Sans" ”1’24”";va ”Vi v?"l.'~"7’fi-' I" “I '0'!" ' x“ 4" ~ ‘LM” 31" 445-12.." .2}! ma" ".‘Q':‘:¥131'L'I’J‘:" 3." ’ -. ~ ' ‘ . . I 4‘. up! r.) .o 21*: y‘to I" . ~(‘I II o: I, 6 ‘5 <‘ 1" II fit 4‘ - ‘H 1 r 4 * 'W bu - ‘\ r 4*?” " 'fw 3“ ’15")... : N.Jf;.§y‘ (“V "”1.“ v14, .34: '11 9:14“ .vf;‘1rm',;“¢’vp}. '4'" 1'3"". 49:33“ “23.3"ng ' ‘fi’q‘yfil‘flfi ‘. ;.':‘:l. ”,9: 1) ,,., ‘4? . 315* ,‘ . . ' ”“1”! {19% .054 - TIM-297'» 44“? 5154?.“thalf'I--TI:&€’?’3E'553§W!3'r: 11%} 1-9; (25%? “’35:".‘5 {bl‘fzeaficfit‘afi-';"4::L?!ri'..- 4“" ' a...“ 9 '91: Mumswmmw - .42 2 up 49-: New... .94. 4299..» . wwwk I" a. 9 ”"4 if :9 “445.433.5947.. . “2:: I» T 445-449;: . - 5 4-r;.-:"~m“:wflvw;:4*~~3.2‘ ; I} l' 1", . ’ ’ ”.04 i: 34" ‘1‘" ' f 1’. ‘.' of. ;‘~‘. J". * .- '4‘. , "in"... ‘. "k“.' J -‘ * l . PM": 4:3”?! $1 $51 92:;qu ' 35 : ‘Rfi'éfflf‘yti ‘ HEW? 03%;} 5"? 91:14 .(3‘5. ngg-Ié‘uw " 11$); giffiu1?3£ir-ng; 33““? . .' m. Fr”, ' :. 1-1 '4“ ' n. .1' '3 ‘ .' "d ‘ ' u . 40"8’u .. ‘ ' i". '.' r." 4:14"! «7‘ :r'g‘ 24'. '“I ' 'ru 9. -- : 4R3“ ' * .'..:-‘ " I J". 1““.‘r "u. .9 2.94%.? " {I {"1}; 2% ”I"?! “‘3'? 34155?Pwlg-a:-§4'~'§§Tb5f§é§fl5f~lx’7nfi‘g§".a§9|“fiié3%$fl;§?' ‘g‘f‘fi'lfiawk‘iifzmcv‘. “I! '~ ‘4 245;} "3 m 41‘.“ e4; 2‘.; f 4x; s,“ a”; . 1“- 9"," 924;":1nn'. raw 4.? .u-T “-1" 44:29.4. ”Mm-4:; $317 7453 .41» 3 4, .1 I - .. . A .. 47:: Tab”) ‘ V" "31, .) Fb‘?‘ 4 ‘1‘, 1‘“. "79.2”“ e'k‘"':‘4'o".“ \t' "“"I'b' 29134?“ y w ’0. '4‘ 44’ In E:- .g 3' ' - ‘ I By- ' . .4 ‘1‘ ‘ ‘ q . ’1': 1.:fél’ ‘. 1).“: - '11:; ’1... f."’,“ “ ,’.-‘4"'. ‘ \9“r1 5“,. 4'.“"!& 4 fi. P‘-'..‘mfl9‘-“ ,.. Ib‘ Wli“... 4 '1' .r' 4 .. I, T 44....444 .9 in ., w» .4 9w t r .9944 4.4 ‘24,: ”av-'14“ 1.9.44. «rm 9- "If T?" “"9946“ I 4‘5’139-9 "“144“ WWII"? '52 @494” 39? «a... 5‘44 ‘4. :4- 4:914“ ' fiéfiifii$’.'.4r-3 T - ‘;‘ O “21‘ I . ”lay ' 6" 1 1;. k; , $3.14“. 1.1.4.; 0;" .c “I, <5" 9 ".o‘..4 0L '3 I: " . fl -. - ”.4 ~ ".3 'w.)h..., “:3; ,1, 125;” T‘z, ‘f 9.; i‘ "2 ' 2;}? 44,4444; .5 #11154? 113.. ‘ "x- ”1351.. \WQ‘If Ifi.~¥m~ 2;; . . “‘1‘. arh‘fi: $91"; 19:”): 214,742! ‘ -..;E J" :‘WJEkEi }ff:é 1;?“ 1;; ~ $?{1‘:A'.2‘{L%§5,. e;,:;.: :5.".,:i ”Us”: ’12“; 4:3‘31; FHI” erll*fi;b‘;y§é$§uvfih ,l."_ .L ‘ 2 .u'..'.‘ .‘ , Al.’ ‘ ‘ ‘3. D', .' ‘1‘.” v: “3"“? “a "5‘ (“1153' ' '74“. . yr? '11.“... ”kw/41“, s L! g :qfilJLfil‘ ' 3. {)L‘ "4 ’364 '11..." , 1:92;“! kfi'm a. “23%” 331'“. 1: 3:14.14; «L 53,; ‘23:)" .31, ' i"? 39"???”3'3‘9’197’4‘ I‘. w“ a 14? 11.12“" ' 4; I?" "4'19“”??J1‘d4'w"; ' 33* #3:}:1'533 fl.” “74‘7145’15‘ ,1. \“3'43‘c . I .. x T. A I . ",lfv. “ ‘ ' .‘j‘. "'i' ‘ . ' ‘- '. "wr ( \‘l . m In ‘ ‘0"'." ‘19,; I . 'I .l ZJ;)£‘:"J}‘3“.1;5)(”“4132 55;?M: W4. ‘ . . at "3"": $0???" $74..“ :i‘gqi. ‘ 14;, ’: figdg I’m-'1 4'”: if 14 Wt! gt}. ’3']; *ufisa‘gz‘fi ?;~$$:o;i . ‘52 J“ Am ‘9‘ .‘I .3-1' . ' '7": ‘9‘ "w, *4?- 4‘.) I " ’ h- M: " ”v.34: . 1’ ' . #29:: .4149 1“ 4.44.4999f’a4 «‘3... I :44... ‘ . 2‘. " T ”:99“; 4.. WT ‘ s. 9?»: .49.: 4.9:. ' ° ~ -,;: WEI: "' .. 31,." u“ 412'. .," . - 5"» 31"?!“ .11" 3 “t ,. 3,1, "‘ VJ: 'nq‘w 42," -- :- . . «MM Aim" ' t "4‘ .9 ,. .- . ;. :3 91.4: I: z I?“ “537... ’4“ ’ -. 50"“13'.£ I" ‘4 . xhl”‘ "-‘JinFfifi' 4. .- H “r, ,' .' -. J‘, . _ -‘ 1'}. 31:13.1 )x,‘ 1:412; “ii-d [2‘ K" 1 4 ‘1‘. Wk 04 {1, 1’ . ' '5. I" , .. . 112g ’1‘ J, \jfl. -; . ‘f’fi .ni"!-‘J'.¥T"I“" :3" 5"}, film‘,fio'h; 1:14;“? n’.’ 1 4. ' 4 3 ' I i u 41' ?§'x:.".'o«'*'.‘.-Iaxii’c‘WQfiJ' . ‘ '09:}; " ' ~ {“19” . . *4;¥:p“5,:v,,l1~‘${l."1 :‘l' 'I' ‘ ‘ ' “E." r '. .5&:§'L."‘;'37 w“... 4:} $43!- “:1 94 99.1.», I fl.)",fimu ‘ 2'» - rz" - LM‘ .' W “w "9:4- ‘fiw w‘ 944:4 24444:; .4. s .4 u. .\'f". A I , "‘. "1'73. 9" {-53 I .3 'l- 4,‘ ... J‘- 7%? '43:??? Est-9:99? 'I';.’-’*”'-""."'EL 4's“: .9? =5}"*?7:;iat:y‘a‘.'.'fI-f‘lt‘“ 5-5: 4' “K- sh: 5 v z",,.~-.:x"...; 444,.-u.=,~:zc‘,;-..J:‘ ' ’fi‘y-ofi'ga‘n'fi? arm, :I " .. . " ' ’r ,‘h‘btifi-I 219234 4955.192? -'-?Q“->:h"4: 4; ' ' .' . -. . . _ A4, 4.1.}, 1......” w}. J}. .‘ . ‘.¢4“,.§;‘f' ‘_ .1, ' ,. '," .‘v ;'; a, 4 .. -.. .,--I_r ‘.., . . , .‘j . ’5. ' .1 . I Q 'V ' 3 . "I. . ? ‘K .A 5;),I‘;':J :1! ,.l ' ’IC‘ . D .v'7:§: ’. v":~' ‘4‘ Q. ‘ C y ' 7. ””32." . I -' , o' 3394:5113” . 0;}. ' "H" Hg, {4 ‘ P-w '. - " P $3?" 2 $§.1_2‘4-§?i{545-y..éihv' I. 'x‘ “ ~ ‘\‘h*. 3 a 4 Q ‘34.." ... . w. ' . 9 ~.'-. 4“*§~"" Jr"! - . 3 Jo. ‘4‘ I k. '. To. ' 1.1." .D . .. I‘ \{ytzn ,h. . ‘1‘ D- ‘g c» ‘ V01’5 v..-"~' .' I... "y 4 I ‘ ‘ ‘-' : '5‘5 f-‘H. up ""2“ '. ‘4'“... 'I-‘X~ 1448!"! " ’A' .J; * V 3' H, ~uIl..(.' \.foh1 ‘” 0.; a s. '7‘ “-34.54.“ 4.“ .\. I’ u ’0‘ .J .- 'f ‘33)): ¢.¢~.s‘$ ‘ 'ij‘h ‘4“"41 hr in ... ~ .3" .I‘ I“; ‘-~‘. I ' . “ 4. “w .— - .. . . .- .47 “qfl-fié‘n’iff-‘f: q."- , ' :9. , ' 1-. g . ~ ‘ , - . f ' ,v . , . I , ‘ .,. . 24-4.}. ': . ‘\.'-€J°‘"’z 2.! ”o ' . ‘ ' -- ' '3‘ ‘c._ ‘4.” _ _ ‘N‘. "41234358. '4 .. , _ .' d‘ L. A 4 -.“r~3\'..,;‘i‘_ _ .1 .._ .1‘.~.1, 4. - I _ I 4-,». .- w. 4. , 2-: . ‘3 M ~ 3"\ ("n !‘ lg‘i . .‘1'. ,r-f . 2.2.1? ’94») 4“; f. '. I I .' Q '.' 'l; '. '. n) .. ' . ~ ““3 {i}. '7 . ' «I 4' : .‘ r- ' O ‘44 " v . , ‘ ‘ 1 . ,_ 1. . . O. '~‘ ' ’ fl'uiw ., 1 I _ A '\ .- ,1 ‘ " h:a;§3..~’.£;, 4 ,2- .. 5“,}, , - s . _ 3.‘ 4. . .. ‘1 . ..-;‘... ." “ppm“. . '3‘“ ‘%-"«~'~;=‘3“ «(441,; ._ u .514.» . 5:1":32 54“ . '-_ ‘y. . _ 4“.“5‘7“. -.":-.‘. Io '1'":.‘n.'!r ,hu iL‘Ia‘v-q ' , ' \' 4' . , . '1 [Ur Q“ 'q . - . .. ' «'1. 3“"1'”r“gf"-H‘tu‘h~ 7" . M" 'L" t _ I.. . new. 9.”. 3-5.. .. , --’ -- 4% .9 , -~, ._ ,. " ‘04“. '-¢.,. ”Wk. ‘ .- '. ‘.W-.."-‘ , _ . ‘ .,. 4 .' . b . ‘ . 4 "..'" :0.I 3'..."‘&"- _ I "' O, ' ‘(.'.:;;H“:. '21?» I: ". ‘g: "‘ w " .:n'.v '.‘., ' ' b ‘ g ‘ fl“; ‘0', 3, ~94 “ u ‘4 fl a r ‘4 ‘- .‘ . ‘C. 'Q. '- ._ ‘ “u “l . ”4 ”’3" '6”.II"‘":“‘::&~.°;~ 4-3:. 2*. ' N“. 1 u";‘-: (2319' N. ‘ 0" \g."'::l 5" ‘ ' ’ ~.:...::vav"'.‘: \“.:$h:“" gu‘u‘ .. o 4".'.‘.".l.~|" -. "~"\A"y‘r' ., ' 24‘" ‘ ‘0, . 4-. ' ' ‘1 ‘ '98- ' 5 " ~. w‘s D ‘fi 1. ”2.. )‘h u, ... ~. ‘0 . ( - u ‘ ' 0‘ ”‘(':"1"'..J-"?'Q‘r s? "H” “4‘" math” . h - , .' L94,“ » .‘s 'w v. u M: «\i-. ‘1"~.~. In _ . fv.‘5'~ H .‘pff‘v. 1“."4‘44 ,‘ _'.“.. .'.". ‘x'._“\ ”g 'nflv“ . ..fiv. ' - ‘ .' ' , 'vJN. .‘u'J‘ ' ‘ '1 ”‘00 .4. t ‘ w... ‘ 34“ 2:. ’5‘..'N: ‘ ‘1" IO. M "7“ “s ' 4 .6 ' t," ”.10";- "P.."\.,: fiioJ-PYQK'V f? V. . . . - . . ‘W' Pu" .75' Q .‘. h ‘Wb“-~~v’. ' ‘-' ‘0‘. ‘. ~ ., .. y .. _ . ' . .v.‘b .. ‘4, .u. 4 '0 p- ’ ' ‘v A . ”'4‘ c”... .9", I . 1-, -4 ”4‘ n. 3,;- ~§z.,-“:.;1 .§;~;4_'.,h_,!, -.,;-~‘.‘- " u '.' .- ' SI" '- ‘9. ‘ ' ‘ ' -"" "3 4' t.‘ r- W I . " 1 r. “4“» . Viv-3‘3“ 73‘2'"‘4:L’é"'3""~:" ". 3 ,.._.O‘_".'.I:l.>.. ' I , .... l‘ .. ~.- I. I ' 4“” 75:45.". ' . "‘4‘ u' n“ . ‘ 3". ‘l‘h'.. ' ‘2‘. 5",- v ..‘.-.‘ . -" ‘ “94"“,“1; ‘ .‘~u..' V». '5‘}, ' ;, l‘é‘tfl.9.‘."fi‘¢,, N03"? ‘ \ffléihc-Q" ~ (p' n,‘."."'. .q I" y. E. .'.-:V‘,.“_ ‘A! :~. 3"" -,‘ 3‘. lu‘.._‘ NH, ‘.’;\‘ a." .... r‘ 4 5"", .h\ . "I “u ;. .'~' 4 u ‘. 9 IE" 0. run- ‘b"4.-"'.' ..“~;"."r'. . .. 4.3.»-‘w -- 1:431" - T 4.....- -" "-' ‘f-és'quuv“ " "3-2:" "'- ._“‘:, b, .‘b' u' c. 1". o . .34.‘ “I". .4 .k 4,, 4. n. ."0- ~‘ ' .-, ”3"; - .._. '4‘.“".“ on ,9...” '9' 9" "4t 0 4 , ' ‘- .. - ‘5. I. . a ‘4 “I? ..‘I .‘thJ . .\ ° :4~~. \ .~ v‘u “Q‘J'Pe w, v," . 4 . -,-7 _ .g:. . 4‘. ;.'.:.-. x.- -9 ‘4. . \ Q, ,~ 1 _" :V'I‘ml‘ ‘4‘. .1 "'\‘~":A~s 1“ .‘c‘ . - '~"."~ "\~‘ ‘ h x , 1%. ‘u. '- - o. .‘\ - s“‘\-fi . _, '0. s . -§. \, ' *4 “ ‘0- .5,- '57 . "i"; 1 g” t -» ~ 4" l"! . . . .- ' ‘- "|.'.. V‘ ‘ . s 4 h, . w .s. - .- . g" ' " ' - "‘v’ . . H a . ‘0 ‘9 ‘4'. I .\ 5,.“5‘NQ I “u \ .' . '4-“‘4'N\ ' K "‘5 '5‘" o ‘. 5," ‘ 4“'A ' ‘N o "0‘ . . ‘4! ' .0. 4 ' ..“~.‘.. .4 ,. a '0 v . q” o . I ‘5 1 . VI 5 t x g 0 4 .V'. . "U'n""‘t " [5. ‘1 .‘LL 4‘... n, ', -..:~‘ . ' l “"v. 1- '._444 -1 v'4u C .v v‘~". ‘0 “'v ". '5‘5‘ 1. . . ‘\ V . ' “I“ f" 1 '39,? 0‘: ---.-'-- 4 .- ‘w-,\ '4'? f‘ '~\'V .. 4".“ ..V‘~ r.‘.'..> "~~‘ .‘ ~I._. 1:1 I‘; I. .‘N .|‘:' T I .14, -..'4.’ '4. ‘4‘ 4." 5:: o ‘2 2‘." ‘ "‘- ' 0'" ~'\v '5 . ‘..'.. 'u. m ,'\. .. ' "~ ‘w" Y- 4 o ‘. " \ ' ‘D "s." - s." Vs ’0‘ ' ‘ ut'v‘m 4%"; -. -i.'t‘- 5“17 ‘ "‘5' . f...‘ k I I, ~,; ‘. ' .10... ' .‘~ :" . b '."\‘1‘ ."‘~’ v. .' ‘.‘.;'~" ‘ 9 '. k‘ " . 3"“. ‘ '. ‘0 1 a... -'.I"- ’1' . PI .‘hi‘- .. '4 ‘ 0 ' :l‘xé ‘5 ”2“ ‘ “.u ;V01‘§‘_‘,' ?. .” ~’:c:-v‘ ‘. 5...... “RH; - ‘ "231's“. L“ “£43 . ‘ “4:0 ' ~vz~ .. '~.':'- 4 .. 5'. --. M 'm‘t‘ w.“ -..\."n‘ I' h. -' ‘4 «I'wh‘ ~-" g - a n .. t . . 0‘ . . ' ~._ . '4...;.,‘; 1'. 4L3. - .f‘., ;~-v_voj ”'"w’. '1'- ‘. 1 . ~ ,» . . ,. I 4 4 ~ , . . - ‘a;‘-. .5: ".' v.9..fi.-. L‘ ‘4', ;..Jv';‘.‘ ' :°‘ "Nb‘ ‘0 . Q“ ‘ .‘ ‘ I . ‘ . ‘_ 4‘ k ‘4 a A' ‘ ““\ ‘ ‘ "' v ”'3‘. ”Is. 1-,04 (3.1.x n. 0. :f‘ 7.. 'g ' . - o-mf'. 2‘ 74.3. ;~-~'.~' Qu: -‘ ‘5.“ “"' Tfi‘ ‘ ., ..~." ~24-‘H'v ..-- —. -..--.. "4' 4.. m, ‘ 4 H. ~."- 4. .’ “0 ' .‘n' -."~ '~" "I" M. '_ . - \ ,' ‘ a 5‘0 . I Q '1'» ‘9‘. . 0' ,~ 1 “‘5. u. ,I. w- .j“- ‘-." . t \n‘fi . "-2 ‘~ ». 3 ‘IC . 'x'“ 9‘ ‘ k" " ”.0... , . , '- .- 44:14. 4 " ' . . ' . . ' . a .. -° L'%:v.“‘..-~".:“ "-""-“"‘ " 4 J" '.' I ' k‘ ".‘".s'v.L“ , 'u‘“.\ . 5“ ‘ - c‘ H‘ h ' u p "n . ‘ " T ' a 5’ |.' g g ‘0 ‘ - ' \ . ~44? '. . W‘ , 4 I 5 . f ‘, . ‘4 b 4‘- ‘ ' ‘ . - . 4». ‘.~. ~.- .~ - ' --‘.‘~.:‘« -~ = ** .-. I :Dv:_‘ 1...; ‘g .‘ -' .. _ . . . ‘C “ .l‘.‘ 4 9 . 'I' ‘| u' . ‘ ~ . '9 - I . 4, '- ‘ ‘ .* 4-.-vv,’ ‘ ‘ _. v \ '4 ' h . '1 ..O Q. N 9 o.‘ - “v n ‘ V; ~X.- '. . K .1, . x s - . .‘m .. ~ I ... . " ‘.'*.»,'.'-.."?"t‘-' I ‘ “'- " " "k‘r.‘.' o . ..4 , .. . . n .. , . a . .h\o_“"”'. ‘0 I' ‘0" ‘..' "I“ -W“ “ A '- ': . In ‘54 ' .‘:"'4. "~‘ - -'.."'"."- ..-. u ' '9. ‘ 11‘ .' :Y'Jk. - I ..-. ‘- - 9. "‘ '. o . ‘ - ' l ‘ 4 0 ‘H...: -.’s a W. fi"~ .‘ .4 - 4‘s ‘. ‘ I‘ Q h .': : g r . s .- I - - . ‘ -. - ‘- ‘ . " l ‘ "o ‘ '0' I'. ‘Q I .-‘=Il.~.l 4“ '5 ‘ ’L.‘. .— ‘ ‘ .' " - _ . - 0. V- ‘ ‘ ‘ - "‘ - " . .z‘ .. ‘.$'V.1 A... .. br‘ .\__ ‘.,_'- .. .. ‘ ¢ ' ' . 1g". ‘.;‘ :1" ‘1‘ 9. ‘ ‘g ‘s ‘7 ‘u.’_‘.. ‘d ‘ | . ‘ I . . o - Y .‘ . 7 5 .§ *4 , p . Q a , 4 - a; _ .1. . l -";"I, r 3' Ms; ‘ I ~ ". 'a‘. V?:“-.“- \. I._ >.§-" 5, .1‘.‘ _.‘-‘.\_.'..'.. v.;. ._‘ ‘—-..‘|' y. 1‘- R's ‘4 N1“.‘; . ‘ O C1.IQ X \I‘... I”!”WWII!lllflllflllllllfl”IIIIHNIIHIINHHHHII 53 8869 . ‘ - § ' - ‘ - ' ‘ _—, h - - ‘ ‘ . C - - . .. ‘4 . 4 .5“ __ - _. 4 .—'- ~ _ b ‘ ’ _ 'n “ ’- » 1 .— .'.- J=_,=1_‘§(-l,' ' -. - - n )A 1 ‘ _ — _ _ _ .- 3. _ 'fi4‘L“ 'v ' -‘ L- ‘ \’ - .1 a» - ' — A A; . A- g: A_'v_77?r:f‘ "‘9‘ h.~:(’k’~ A.\ w :\-. ““ - v ‘ - ~.~--_ — r-‘A ‘-.- 4 A. _ -. A r. .¢.~‘- _l .. ____--. —~..- -..~‘ - “‘3‘ .' ,__-( ‘7 __. 5... “y... PLACE IN RETURN BOX to roman this checkout from your record. TO AVOID FINES return on or before data duo. MSU Is An Affirmative Action/Equal Opportunity Instituion Warns-9.1 IIE5; PYTI‘EIIIFHIII n IV INVOLUTION OF TTIE UTERINE MUCOSA IN THE EYE REVOLUTION OF THE UTERIm MUCOSA IN TH}: m TEES IS Submitted to the Faculty of the Michigan State College in partial fulfillment of the requirements for the degree of Master of Science in Animal Pathology by Andrew Waldmere Uren bur-V ‘ June, 1934 THESKS CONTENTS Review of Literature Hon-pregnant Uterus Pregnant Uterus Involution of the Hucosa of the Ewe's Uterus Summary of Involution in the Mucosa of the Ewe's Uterus Tables (3) Bibliography Photomicrographs (42) Acknowledgment eaten Page 58 involution of the Uterine mucosa in the Ewe neview of Literature Detailed descriptions of the histOlogical Changes taking place in the mucosa of the bov1ne or ov1ne uterus during involution are lacking in veterinary literature. Statements on this important subject in our early veteri- nary literature are based on observations of the involu- tion of the uterus in the human. Our knowledge concerning involution of the uterus can be said to start with the work of Friedlgnder (l) on the uterus in women, followed by Kundret and Engelman (2) and Leopold (3). These early investigations have been followed by a long list of articles by different workers dealing with the subject in women. The uterus in women is of the decidual type in that a part of the mucosa of the uterus, which has undergone certain changes to fit it for the implantation and nutri- tion of the ovum, is cast off after labor. A thin layer of decidual tissue is cast off with the foetal membranes immediately after birth. The remaining mucosal cells be- come differentiated into two layers; the one adjoining the uterine cavity is decidual, becomes necrotic, and is cast off in the lochia, while the other layer adjoining 2 the muscularis and containing the fundi of the glands, remains in situ and constitutes the matrix from which the new endometrium is regenerated. in lUSl there appeared an article by J. whitridge Williams (4) on a series of uteri taken from women who had died from causes other than puerperal infections,and uninfected uteri amputated during the puerperium from women suffering from chronic nephritis, serious heart dis- eases, etc. His material was thus not complicated by le- sions associated with infections or the uterus and there- fore meets the often made complaint that unless the stu- dies were nsde on normal uteri, the conclusions would prob- ably be incorrect. Williams (4) shows the intricate changes involved in the regeneration of the uterine mucosa following delivery. in doing so he advances some new contentions concerning the process. He states, "It seems to me that the evi- dance thus far adduced makes three points clear: first, that the process is in no way connected with inflammatory change; second, that there is no indication of any exten- sive necrotic process; and third, that all of the speci- mens show unusual proliferation of endcmetrial tissue, which does not merely cover the surface of the placental site, but invades it in all directions, but particularly extends between it and the underlying muscularis, no that in a general way it undermines the placental site 3 and ultimately leads to its extrusion or exfoliation.” He further states, "Regarded from another point of view, such a process of exfoliation should be regarded as very conservative, and as a wise provision on the part of Nature; otherwise great difficulty might be experienced in getting rid of the obliterated arteries and organized thrombi, Which if they remained in situ would soon con- vert a considerable part of the mucosa into a mass of scar tissue, with the result that after a few pregnan- cies it would not longer be possible for it to go through its usual cycle of changes, and the reproductive career would come to an untimely and." While the ewe has the multiple type of placenta and is not a deciduate in the sense that there is discarded along with the chorion a portion of the endometrium, the ewe is a deciduate in that the cells that proliferated to form the crypts or maternal placenta of pregnancy are disposed of postpartum in a somewhat similar manner to that described by Williams(4). Fleming (5) does not describe the changes that occur in the uterus postpartum. He merely states that after the foetal villi are withdrawn after birth the cotyledons are shed or disappear in some obscure manner. DeBruin (6) does not describe the complex changes that take place in involution. He states, "The uterine mucosa after parturition also surfers considerable change. 4 The cotyledons become smaller, lose their peduncular iden- tity and undergo regressive fatty metamorphosis. Fourteen days later cotyledons proper do not exist. After three weeks the mucosa has returned to its original state. Puer- peral processes - for instance, septic metritis - do not influence the regressive changes of the cotyledons; that is they do not retard them.” In 1908 appeared the comprehensive article of Hilty (7) the third part of which, dealing with the changes in the mucosa of the uterus of the cow during the puerperium, is of interest to us. He states, "With cessation of the blood circulation in the maternal and foetal placentae and the loosening of the afterbirth, and onset of postpartum pains, the regenerative processes in the uterine mucosa and caruncles begin.” "The caruncle undergoes throughout its entire extent a fatty degeneration, setting in at its periphery. Crypts and crypt walls vanish. The maternal placenta becomes a stnuctureless mass of cellular debris which disappears be- tween the tenth and fourteenth day postpartum, that is to say, it forms an essential component part of the~ lochia, consisting of uterine epithelia, leucocytes, and fat drOp- lets.” Hilty (7) goes on to explain that after the mater- nal placenta has been cast off in the lochia, the cellular stratum or subepithelial tissue develops by intensive cell 5 proliferation into cap-shaped, melon-like puerperal carun- cles, towering above the mucosa. These caruncles are then covered by epithelia Spreading over the caruncle from the inter-caruncular epithelium. The puerperal caruncle then corresponds to its original juvenile caruncle. In 1924 appeared Hallman's (8) article on diseases of the reproductive organs of cattle. He describes the histo- logical changes occurring in the cotyledon of pregnancy. His conclusions agree with Hilty's in that the maternal placenta is eliminated down to the connective tissue band or cellular stratum at the base of the maternal placenta. In Hallman's series of cases sufficient material unfortu- nately was not available to cover the full period of in- volution. The latest case studied was twelve days post- partum, and the involution was not complete. Williams, W. L. (9) wrote an article in 1929 on "The Significance of Utero-chorionic Lesions in the Cow," in which he reviews a group of papers by Bellman and his col- leagues, and Williams and his colleagues. In describing the involution of the maternal placenta or cotyledon of Hilty (the crypt mass) Williams states, "After the ter- mination of pregnancy the mass of crypts constitutes a useless tissue which is eliminated. Having lost their epi- thelial covering, an extensive denuded surface results, freely exposed to any bacterial or other irritants present. The tissue of the crypt walls consists to an unusual de- gree of blood, lymph and other liquid, and immediately the 6 afterbirth comes away the healthy uterus contracts with great rapidity; the unnecessary fluid and movable cells are abruptly withdrawn and the cotyledon of Hilty (the crypt mass) is very largely returned to the body as a whole. inevitably, as in a wound, some of the exposed superficial cells perish but the amount is very small in typically healthy cows and no clinically visible discharge follows the expulsion of the afterbirth. The line of de- marcation between health and disease can not be accurate- ly drawn, but the Williams group, from the clinical stand- point, locates that line far nearer to an absence of rec- ognizable discharge than does the hallman group from .the laboratory standpoint. "The caruncle of hilty does not disappear after healthy parturition, the cellular layer, 2, in Fig. 7, re- mains intact, prepared fully to provide new crypts in the next pregnancy. While histologists have not yet discover- ed the structural basis of the observed phenomenon, there is apparently some fundamental arrangement and function of the cells in the cellular layer, 2, Fig. 7, which preor- dains the arrangement and character of the uterine crypts and these fix the character of the chorionic villi<3r tufts. The exact extent of injury required to disturb the symme- try of the crypts in the next pregnancy is unknown, but the evidence indicates that the lesions need not be very profound." Williams first says that the mass of crypts consti- tutes a useless tissue which is eliminated, and then goes on to say that the cotyledon of Hilty (the crypt mass) is very largely returned to the body as a whole. These state- ments contradict each other We do not believe there is any histological evidence to show that there is apparently some fundamental arrangement and function of the cells in the cellular layer of the caruncle which preordains the arrangement and character of the uterine crypts, and that these fix the character of the chorionic villi or tufts. In fact, there is evidence to the contrary, which will be cited in the short description of the evolution of the uterine mucosa. Non-pregnant Uterus The uterus because of its variability is one of the most interesting, as well as the most difficult, organs to study. As the shape and topographical relations are suffi- ciently described in the standard texts on anatomy, this paper will be confined principally to the histology of the mucosa. Some confusion exists in veterinary literature in re- gard to the use of the terms caruncle and cotyledon. The terms have been applied by some writers to the mass of 8 cells that constitute the raised circumscribed areas in the non-pregnant uterus, and to the much larger mass that develOps in the gravid uterus from these raised areas. in this paper the raised areas in the mucosa of the non-pregnant uterus will be called caruncles or placene jg; matrices. We prefer the term "placental matrices" since the raised areas are composed of permanent cells which do not remain grouped in a caruncular shaped mass in the cotyledon of pregnancy. The term cotyledon will only be applied to the semi- spherical shaped bodies that develop in the gravid uterus and are composed of the permanent placental matrix cells, which spread out into a band of cells in the cotyledon, and the decidual cells that proliferate from the matrix forming the crypts. The terms 23123 2332 and maternal placenta will be used synonymously and will designate only the decidual cells of the cotyledon. The term foetal lacenta, or chorionic ziili will be used to designate that part of the chorion which is lodged in the crypts of the maternal placenta during preg- nancy. The chorionic villi in conjunction with the decid- ual cells of the crypt walls that lodge the villi during pregnancy effect the passage of waste products from the blood of the foetus into the blood of the mother, and of ' 9 oxygen and nutritive materials from the blood of the mother to the blood of the foetus. The term glandular mucosa will be used to designate all of the mucosa containing glands - namely that which is not occupied by the caruncles in the non-pregnant uter- us, and all of the mucosa that is not occupied by the coty- ledons in the pregnant or involuting uterus. Histology of the mucosa of a Non-pregnant Uterus Ewe 8U4l Non-pregnant This ewe, a non-pregnant, five or six-sear old ani- mal, was Killed May 15, 1932. All of the generative tract was removed as soon as possible after death and placed dor- sal side up on a piece of cardboard. The internal os of the cervix was located by palpation through the wall of the uterus and measurements taken of the length of the horns from the internal 05 around the greater curvature of the horns to their tips. The diameters of the horns were always measured at their greatest diameter. The right horn measures 115 millimeters in length and 12 millimeters at its greatest diameter. The left horn measures 120 millimeters in length and 12 millimeters at its greatest diameter. An incision was made through the dorso-median line of the vagina, cervix, and around the greater curvature of the horns, thus exposing the epithelial surface. The edges 1U of the incision were pinned down to the cardboard which flattened out the hollow organ into one plane. Data were taken on the gross appearance of the mucosa and a photo- graph of the uterus was made. The whole genital tract was then fixed in Houin's solution for twelve hours, when it was possible to cut blocks of tissue without disturbing the relationship of parts. The blocks of tissue were lateled and fixed long- er if necessary. They were then run through the alcohols, cleared in cedar wood oil, embedded in paraffin, sectioned and stained in hemetoxylin and eosin. macroscopically the endometrial surface of the mucosa is differentiated into two parts, i.e., the caruncles and the glandular mucosa. One hundred and twelve caruncles are present in this uterus. The caruncles are arranged in four symmetrical rows in each horn; the rows running parallel with the long axis of the horns. in the middle and lower part of the horns the caruncles are elliptical in Shape but become cir- cular toward the ovarian and of the horns (Fig. l). The caruncles project about two millimeters above the glandu- lar mucosa. During the resting period when the uterus is not sub- ject to the cyclic changes of estrus the epithelium has a grayish white translucent color. During the rutting sea- son when the uterus is going through the cyclic changes of ll estrum the caruncles may be black in color, due to a pig- ment formed under the epithelium, Marshall (lo), Casida and McKenzie (11). We have also noted the black pigment under the epithelium in the glandular mucosa in some of the non-pregnant uteri examined during the rutting season. Hilty mentions the pigment occurring around the edges of the caruncles in the involuted uterus of the cow. Hammond (12) also mentions an amorphous brownish pigment that ap- pears around the caruncles seventy-two hours to eight days after the beginning of heat in the cow. Macrosc0pically there is nothing to distinguish the glandular mucosa from the caruncles except that the carun- cles are elevated above it. Histology of the Glandular Mucosa The wnole surface of the mucosa is covered by an epi- thelium of columnar cells which is continuous over both the glandular mucosa and the caruncles. This epithelium dips down in the glandular mucosa, at frequent intervals, to form the uterine glands which are much branched toward the fundus of the glands. The epithelium or the mucosa is but one cell in thickness. These cells have large oval nuclei that are situated near their bases. Just below the epithelium is a shallow layer of con- nective tissue densely crOWded with nuclei whiCh are 12 elongated and lie parallel to the epithelial surface. Nu- merous leucocytes may be scattered through this layer. This connective tissue layer is richly supplied with cap- illaries and small blood vessels. Beneath this layer is a much thicker layer of looser connective tissue which reaches to the inner surface of the muscular wall of the uterus. This layer of loose con- nective tissue is continuous with the whole inner muscular wall of the uterus as there is a layer or this tissue be- tween the caruncles and the muscular well. The connective tissue cells of this loose layer are similar to the cells in the layer under the epithelium except that the nuclei are farther apart and the cells have branching processes which anastomose with one another. The whole layer is penetrated by capillaries with the larger blood vessels lying in the deeper parts. Hamifying throughout the layer are the uterine glands, the fundi of which reach to the inner surface of the muscular wall. The fundi of some of the glands ramify in the layer of loose connective tissue below the caruncles. The excretory ducts from these glands do not pass through the stroma of the caruncles in reaching the lumen of the uterus, but pass to the side of the caruncles and open on the epithelium of the glandular mucosa between the caruncles. The epithelial cells lining the glands are continuous with the epithelial cells covering the mucosa. No histo- 13 IOgical difference can be seen between the epithelial cells lining the glands and those covering the mucosa. Histology of the Caruncles The caruncles are local thickenings of the layer of densely cellular connective tissue found just below the epithelium in the glandular mucosa. As already mentioned, they are covered with a single layer of columnar epithe- lial cells which are continuous with the epithelium cover- ing the glandular mucosa. The dense cellular tissue of the caruncles is com- posed of cells with elongated nuclei similar to the cells under the epithelium in the glandular mucosa. it is tra- versed with numerous capillaries which usually run at right angles to the epithelial surface. immediately below the caruncle, in the layer of loose connective tissue that is interposed between the caruncle and the muscular wall, is a group of large blood vessels which ensure a rich blood supply to the caruncle should pregnancy take place (Fig. 2). Id The rregnant Uterus The observations reported in this paper are limited to the processes taking place in the involuting mucosa of the ewe's uterus. It would be impossible, however, to make clear the changes that take place during involution without an understanding of the changes that occur in the mucosa during evolution. Assheton (13) in laud published an important article on ”The Morphology of the Ungulate Placenta, particularly the Development of that organ in the Sheep,and notes upon the Placenta of the Elephant and hyrax." Most of the dis- cussion of the changes occurring in the mucosa of the ewe's uterus is based on Assheton's article. The fertilized ovum in the ewe does not reach the uterus until the fourth or fifth day after coition. On the ninth day the zona radiate ruptures and the blasto- cyst for the first time lies in direct contact with the epithelium of the uterus. The wall of the blastocyst from the time expansion begins on the tenth day until the sixteenth day is of two layers, the trophoblast (ectoderm) and hypoblast (entoderm) each of one cell in thickness. The mesoderm soon makes its appearance growing out be- tween the ectoderm and entoderm, and the wall of the blastocyst soon consists of tropnoclast and mesoblast. The first attack upon the epithelium of the uterus 15 occurs about the eighteenth day. The trophOblast, where it comes in contact with the epithelium of the caruncles, becomes slightly thicker. certain binucleata cells of the trophoblast migrate to the surface where they are in contact with the uterine epithelium. These cells insinu- ete themselves between the cells of the uterine epithe- lium and pass down to their base: where they then force themselves between the epithelium.and the sublying matrix. The epithelial cells are cut off from nutrition and soon degenerate. Other phagocytic cells of the trophoblast an- gulf and remove the dead epithelial cells. The matrix of the caruncles is now in contact with the trophoblast. The allantoic splanchnopleure makes its appearance about the fifteenth day and grows very rapidly. 1t fuses with the wall of the blastocyst about the twenty-third to twentysfourth day. The traphcblast, soon after the destruction of the epithelium over the caruncles, forms into ridges over the caruncles. rurrows are formed in the stroms of the ma- trix opposite the ridges of the trophoblast. The future villi of the foetal placenta are formed as buddings along the crests of the ridges, first of the trophoblast which is followed quickly by the mesoblast. The mesoblsst forms the core of the villi and carries the branches of the allantcic blood vessels. The villi grow by their own interstitial growth and the cells of the carun- cle proliferate new cells which grow up around the villi. 16 The walls of the crypts are not lined by epithelial cells of the uterus but by cells from the trepnoblast. Assheton names the layer lining the crypts plasmodi-trOphoblasts. The growth of foetal villi from the chorion with the corresponding growth of crypts from the matrix is a con- tinuous process from the time villi first appear until pregnancy is terminated, as reported by Assneton (13) in the ewe, Hilty (7) hallman (8) and hammond (12) in the cow. As pregnancy advances and more villi develop on the chorion, calling for the deveIOpment of more crypts to lodge the villi, the placental matrix cells do not remain grouped in a caruncular shaped mass but spread out into a thin band of cells to provide for the large number of crypts that form in the cotyledons. 1n Rig. 3, the dark band of closely packed cells around the periphery of the crypts are the placental ma- trix cells indicated at (c). The crypts that result from proliferation of the matrix cells are indicated by the (brace b). As the number of crypts increases and the coty- ledon grows larger it projects into the lumen of the uter- us. The caruncular matrix spreads out into a thin band of cells in the cotyledon by an invagination of the caruncu- lar mass of matrix cells. This results in the adp cent glandular mucosa and its epithelium being carried up the sides of the cotyledon as it increases in size because of its attachment around the edges of the matrix of the carun- cle. These statements are made clearer by referring to 17 Fig. 2. The epithelium between the points (a) and (b) over the caruncle is denuded by the chorion and crypts begin to form on its surface. in Fig. 5 the points (f a f) corre- spond to (a a b) in Fig. 2. if the epithelial surface of the glandular mucosa is followed down the wall of the coty- ledon from.(f & f) on each side, the cotyledon will be found to be attached to the mucosa by a narrow short stem indicated by the (brace g). The chorion is indicated in Fig. 3 at (e, s1, '2' and as). The villi of the chorion enter the cotyledon at (a1). The muscular wall is indica- ted at (d & d1), and the uterine glands at (c). The lacu- nae of extravesated blood formed between the basesof the vil- li and tips of the crypt wall 81‘ indicated at (h). The changes taking place in the glandular mucosa of a pregnant uterus are shown in fig. 4. There has been an enormous increase in area of the lu- men or the uterus. This increase in area has called for a great increase in the number of epithelial cells because the cells have not increased in size. They are still col- umnar with oval nuclei, (Fig. 4, c). Just beneath the epithelium. is the shallow layer of dense connective tissue with elongated nuclei lying paral- lel to the surface. There has been a great change in the uterine glands that ramify in the loose connective tissue layer of the mu- cosa. They have increased enormously in size and occupy 18 nearly all the area in the mucosa (Fig. 4). Here too there has been an enormous increase in the number of se- creting epithelial cells to account for the increase in size of the glands because the cells have not increased in size. (Fig. 4, a). The loose connective tissue of the area appears to be relatively reduced in amount. It is found only be- tween the glands and around the blood vessels. The nu- clei are fewer and farther apart than in the non-preg- nant uterus, (Fig. 4, f). At (a) can be seen a portion of the chorion overlying the glandular mucosa, and at (b) the epithelium of the chorion is indicated. The mus- cular wall of the uterus is indicated at (g). Hilty (7), 1908, Hallman (8), 1983, and Hammond (12) 1987, have reported on the evolution of the uterus in the cow. in the cow the crypt mass does not invaginste as in the sheep to form a cup-like cotyledon. The cells of the matrix become modified into a connective tissue band at the base of the crypt mass. The cotyledons have long stems which are covered by epitheliula Hilty, in describing the formation of the cotyle- don in a six-weeks pregnant bovine uterus, compares the stroms of the placental matrix to the serotina in the human. The crypts are formed by new cell growth from 19 Bellman, in his description of evolution of the bo- vine uterus, shows that the formation of crypts in the cow is due to the stimulation by the chorion in somewhat the same way Assheton describes the ewe. Hellman points out that the cellular connective tissue of the maternal cotyledon (placental matrix) becomes modified to form a continuous band of densely arranged fibres at the base of the cotyledon (crypt mass) beyond which the chorionic villi do not penetrate. Hammond's description of the evolution of the uter- us in the cow agrees with Assheton's description in the ewe. He states there is not room below the surface. of the cotyledon (placental matrix) for all the develOpment which goes on after pregnancy begins and that the tissue of the cotyledon (placental matrix) develOps by growing up into the cavity of the uterus. in Hammond's Opinion the cotyledon \placental ma- trix) causes greater pressure on the foetal membranes over the caruncles, because they are raised above the glandular mucosa and in addition are gland free, so there is no secretion to float off and prevent close ep- position of the chorion with the caruncles. This allows the phagocytic cells of the chorion to function over the caruncles or even in the glandular mucosa if pressure of the foetal fluids becomes great enough. Hammond states, "From a comparison of the number of 20 cotyledon attachments in the pregnant and non-pregnant horns of the uterus, it is apparent that the power, not only of develOping the dormant cotyledons of the uterus, but also of initiating the formation of new adventi- tious cotyledonary growths rests with the foetal mem- bra nee . " Involution of the Mucosa of the Ewe's Uterus The material for this investigation was collected from a group of eighteen ewes killed at various intervals of a few hours up to thirty days following parturition (See Table 1). Technique Used The whole genital tract was carefully removed from the ewe as soon as she was dead and placed dorsal side up on a piece of cardboard. All measurements or the length of the horns were taken from the internal on of the car- vix around the greater curvature to the tip or the horn. The width of the horn was taken at its greatest diameter. The lumen of the vagina, cervix and horns was ex- posed by making sn incision through the dorso-medien line of the vagina, cervix and around the greater curva- ture of the horns. The organs were flattened out and 21 the edges of the uterine wall pinned down to the cardboard. Data were taken of the gross features and photographs made of some of the uteri. The whole genital tract was then fixed in Bouin's so- lution until the tissue was hard enough to cut blocks witn- out disturbing the relationship of parts. Twelve to four- teen blocks of tissue containing a cotyledon or a portion of e cotyledon were taken from each uterus. The blocks were labeled and fixed further if the fixative had not pen- etrated through the block. The blocks of tissue were then run through the alcOhols, cleared in cedar wood oil, imbedded in paraffin, sectioned, and stained with hematoxylin and eosin. Ewe 24, Approximately 12 Hours after Parturition This ewe was Killed at 1:25 r.M. on January 26, 1932. She had dropped twin lambs between 11:00 r.M. on January 25, and 7:00 A.M. on January 26. The foetal membranes had been passed before she was Killed. There is no evidence of any retained foetal membranes in the uterus. A small amount of watery bloody fluid is present in the lumen of the horns, cervix and vagina. The cotyledons are arranged in four parallel rows in each horn. They are farther apart in the middle of the uterus, where the size of the horns was greater during pregnancy, than at the ovarian ends. 22 The crypt mass is visible in the circular-like de- pressions on the summits of the cotyledons which project into the lumen of the uterus. The empty crypts in the cotyledons are plainly visible. The uterine epithelium is bright, wrinkled in appear- ance, and covers the sides of the cotyledons up to where the; crypt formation is visible. Histology of the Glandular Iucosa After parturition several involutionary processes are going on in different parts of the mucosa. The excess epithelial cells are being destroyed by what appears to be a vacuoler degeneration or hydrOpic de- generation. The vacuoles are formed in the protoplasm of the cells and the nuclei are crowded to one side (Fig.7). Vacuolar degeneration of the excess epithelial cells is a gradual process that keeps pace with the decrease in size or the uterus. involution of the uterine glands is a rapid process and is about complete at the end of the fourth or fifth day postpartum. The excess glandular cells that are de- stroyed by vacuoler degeneration are not absorbed in situ but are exfoliated into the lumine of the glands lFig 7, \c). The lumina of the glands are less than half the diameter of those found in the pregnant uterus. 23 in Fig. 4 of the pregnant uterus the glandular muco- sa consists almost entirely of glands. in Fig. 5, approxi- mately twelve hours postpartum uterus, the glands occupy much less of the mucosa and connective tissue is becoming relatively more abundant in the area between the glands. Histology of the cotyledon The cotyledon approximately twelve hours after partu- rition is illustrated in Fig. 5. The decidual crypt mass or maternal placenta with the empty crypts still visible is indicated at (0), Fig.5. The permanent placental matrix cells surround the decid- ual crypt mass and are indicated at (a & b). There is a line of hyaline degeneration on the inner edge of the pla- cental matrix band indicated by the arrow at (d). The mus- cular wall of the uterus is marked (E) with the perito- neum at tF). The epithelium covering the glandular muco- sa is indicated at in). Some of the cells in the wall of the crypts are ne- crotie and a few pyknotic nuclei are present. All of the blood vessels in the area of hyaline degeneration on the inner edge of the placental matrix band, and in the crypt mass, are thrombosed. The formation of this line of hya- line degeneration and the thrombosing of the blood ves- sels that traverse it may be suggestive of the way the on- 24 set of labor is started. There is no evidence of hemorr— hages from the maternal blood vessels in.the crypt mass, Which is additional evidence that the blood vessels are thrombosed. Ewe 8044 Second Day Postpartum.Uterus This ewe lambed at 11:30 A.M. on May 7, 1932. The foetal membranes were passed but were not recovered. The ewe was killed at 10:00 A.M. on May 9, 1932. The right horn measures 590 millimeters in length and 68 millimeters at its greatest diameter. The left horn measures 300 millimeters in length and 47 millimeters at its greatest diameter. Fig. 6 is a photograph of the endometrial surface of the uterus soon after it was opened. There is no evidence of any retained foetal mem; branes in either horn. A small amount of the character- istic thick, tenacious, chocolate—brown exudate is lying on the epithelium. The total number of cotyledons in the uterus is eighty-two, arranged in four parallel rows in each horn and parallel with the long axis of the horn. All of the endometrial surface of the uterus, ex— cept the circular Opening on the summits of the cotyle— dons, appears to be covered with epithelium. The meter- 25 nal placenta can be seen in the cup~like depressions of the cotyledons. The epithelial surface of the glandular mucosa is of pinkish red blood color, while the crypt mass in the cotyledons is of a pale whitish bloodless color. The glandular mucosa between the cotyledons is fluffy and wrinkled due to the numerous rugae formed in the mucosa. Most of the cotyledons are spherical in shape and project from one to one and one-half centimeters above the glandular mucosa. in Fig. 6 the crypt mass of the cotyledon is indicated at (E). Histology of the Glandular Mucose No pronounced change is noted in the glandular muco- as of the second day postpartum.uterus from that already described in the approximately twelve hour postpartum uterus. The excess epithelium covering the glandular mucosa is being destroyed by vacuoler degeneration (Fig. 7). Vacuolar degeneration of the secreting epithelial cells in the uterine glands is not as pronounced as in the pre- vious uterus but the lumina of the glands contain more cellular debris and pyknotic nuclei (Fig. 7, c). As the excess epithelial cells of the glands are destroyed the lumina of the glands decrease in diameter and in this 26 uterus the lumina of some of the glands are about the diam- eter of glands in the non-pregnant uterus. Histology of the Cotyledons Sections through the cotyledons do not show any marked changes from those found in the twelve hour postpartum uterus. As the cells in the walls of the crypts are ne- crosed the lumina of the crypts ,collapse and the crypt walls becomes a mass or coagulated cells and thrombosed blood vessels. Fig. 8 shows the conditiOn of the cotyle- don in the second day postpartum uterus. Nearly all the cells in the crypt walls near the lu- men of the uterus are necrosed (Fig. 8, a). Some of them are pyknotic, others show karyolyais, while in others the chromatin of the nuclei has broken up in irregular deeply stained granules, karyorrhexis.. Necrosis of the cells in the crypt walls does not progress from the line of hyaline degeneration on the in- ner surface of the placental matrix band,(Fig. 8, c), to- ward the lumen of the uterus, but progresses fncm the tips of the crypts bordering the lumen of the uterus toward the matrix band. Fig. 9 is a higher magnification of a portion of a cotyledon showing the permanent placental matrix cells at (A) in the lower right hand corner. The line of hyaline 27 degeneration on the inner edge of the matrix cells is in- dicated at (b), and the decidual crypt cells in the up- per left hand corner at (c). Some of the lumina of the crypts are still cpen. The necrotic tips of some of the chorionic villi that broke off during the expulsion of the chorion, and remained in the crypts, are indicated at (d). Fig. 10 is a still higher magnification of the cen- tral portion of Fig. 9. (A) indicates the placental ma- trix cells, (b) the line of hyaline degeneration,(c) the cells in the walls of the crypts in various stages of de- generation, (d) the necrotic tip of a chorionic villus. Ewe 8035 Third Day Postpartum Uterus This ewe lambed on May 6, 1932 at l:ou P.M. The foe- tal membranes were passed at 4:30 P.M. The ewe was killed on May 9, 1932 at 10:00 A.M. The right horn measures 360 millimeters in length and 03 millimeters at its greatest diameter. The left horn measures 290 millimeters in length and 50 millimeters at its greatest diameter. There is no evidence of any retained foetal membranes in the uterus. A small amount of chocolate-brown exudate is lying on the epithelial surface of the uterus (Fig. 11). 28 The cotyledons are arranged in four rows in each horn as in the previous uterus. The total number of cotyle- dons in the uterus is eighty-six. The cotyledons project above the glandular mucosa from one-half to one centi- meter. The glandular mucosa has the wrinkled, fluffy appear- ance noted in the previous uterus. Histology of the Glandular Mucosa. The involutionary processes as described in the sec- ond day postpartum uterus are in progress in this case. A few of the uterine glands have involuted to the size found in the nonspregnant uterus. Vacuolar degeneration is active in the larger uterine glands. Nearly all of the glands contain cellular debris in their lumina which are remains of the exfoliated epithelial cells (Fig.12,c). The lumina of the blood vessels show reduction in size by proliferation and thickening of the intims as de- scribed by Hilty (7). (Fig. 18, d). Histology of the Cotyledons Sections through the cotyledons show that the invo- lutionary changes described in the previous uterus are progressing. Nearly all of the cells in the crypt walls 29 are necrosed and the lumina of the crypts have collapsed except near the fundi of the crypts, (Fig. 13). in Fig. 13 the placental matrix cells are indicated at (a) with the line of hyaline degeneration indicated by the (brace b). 'The necrotic and degenerating cells of the crypt mass are indicated at (c). Ewe 8043 Fourth day Postpartum This ewe lambed on May 3, 1932 at 9:30 A.M. The foe- tal membranes were passed at 8:00 P.M. She was killed on May 7, 1932 at 9:30 A.M. The right horn measures 420 millimeters in length and 34 millimeters at its greatest diameter. The left horn measures 500 millimeters in length and as millimeters at its greatest diameter. The cotyledons are arranged in four parallel rows in each horn as in previous uteri. The total number is 84. A greater quantity of exudate is in the lumen: of the uterus than in the third day postpartum uterus. The exu- date is cherry red in color instead of the characteristic chocolate brown color nauslly found. rrojecting from the circular Opening on the summits of the cotyledons is the decidual crypt mass which is also cherry red in color. The epithelium of the glandular mucosa is white in color instead of having the reddish color found in previously 30 examined uteri. The orifices of the crypts which were visible in the crypt mass in previously described uteri are not visible in the crypt mess projecting from the summits of the coty- ledons. Histology of the Glandular mucosa The exudate lying on the mucosa contains necrotic cellular debris and portions of thrombosed blood vessels that have been exfoliated from the decidual crypt mass of the cotyledons. The exudate shows invasion by leucocytes from the mucosa. nugae formation on the epithelial sur- face of the glandular mucosa is still pronounced (Fig. 16, e). The excess epithelial cells are being destroyed by vacuoler degeneration. Most of the uterine glands have undergone involution to the size of the glands found in the non-pregnant uterus. 1n the lumine of the glands can be seen cellular debris. Vacuolar degeneration is seen here and there in the uterine glands that are not complete- ly involuted. Proliferation of the intima of the blood vessels shows further reduction in the size of their lumi- na. The glandular mucosa is not as edematous as in pre- vious uteri. la the glands decrease in size there is an apparent increase in the connective tissue between the 31 glands. The mucosa also appears to be more firmly attach- ed to the muscular coat, (Fig. 16, h), Histology of the cotyledon Fig. 14 shows a section through one of the cotyledons. The decidual crypt mass marked (a) can be seen projecting out of the summit of the cotyledon. All of the crypts are collapsed except where a portion of a chorionic villus has broxen off and remained in the crypt, (Fig. 14, g). All of the cells that composed the walls of the crypt are necros- ed, except a few around the periphery of the crypt mass where it comes in contact with the placental matrix band. The placental matrix band is indicated by braces at (b and c), Fig. 14. The dark area around the periphery of the crypt mess and on the inner edge of the placental ma- trix band indicated by the (brace d) in Fig. 14 is the part of the crypt mass which shows invasion by leucocytes. The fact that the necrotic decidual crypt mass is be- ing invaded by leucocytes only in the area bordered by the placental matrix band is further evidence that the blood vessels in the crypt mass are thrombosed,(Fig.14,h). Otherwise the leucocytes would be invading all parts of the necrotic crypt mass from the blood vessels that tra- verse all parts of it. 32 Fig. 15 is a higher magnification of a portion of the cotyledon. The placental matrix cells are indicated at (a). In the upper part of the photomicrograph is the crypt mass (b) with some of the crypts still visible where a portion of a chorionic villus has been retained. in the crypt indicated at (c). The heavy infiltration of leucocytes can be seen at (d). Previous to fixing the uterus in Bouin's sclution, the crypt mass projecting from the summit of one of the cotyledons was grasped with a thumb forceps and with gen~ tle traction pulled out. This was done to determine now firmly the decidual crypt mass is attached to the perma- nent placental matrix cells. Fig. 16 is a photomicro- graph of the cotyledon. The cavity left by the portion of the crypt mass that was removed is indicated at (a). All of the crypt mass in the center of the cotyledon came away down to the permanent placental matrix cells, leaving a clean surface. A small portion of the crypt mass which was not grasped by the forceps remained attached to the placental matrix cells as indicated at (i). This uterus is one of three in the series of eight- een uteri studied in which a heavy infiltration of leuco- cytes was observed. 33 Ewe 8027 Fifth Day Postpartum This ewe lambed on April 23, 1932 at 3:43 F.M. The foetal membranes were passed at 6:43 P.m. She was killed on May 30, 1932 at 10:00 A.M. The right horn is 330 millimeters in length and 60 millimeters at its greatest diameter. The left horn is 490 millimeters in length and 76 millimeters at its greatest diameter. Upon opening the uterus the endometrial surface is found covered with hundreds of retention cysts, (Fig. 17, a). These cysts vary in size from 1 to 8 millimeters in diameter. Eighty-three cotyledons are present in the uterus. They are arranged in four parallel rows in each horn. Most of the cotyledons contain the cup-like depression on their summits. Hanging from the crypt mass in the cotyle- don is what appears to be fragments of chorionic villi. The general appearance of the endometrium gives the impression in this case that involution is not as far ad- vanced as in the fourth day postpartum uterus. Histology of the Glandular Mucosa The involutionary processes are not as far advanced as in the fourth day uterus. This may be due to the large 34 number of retention cysts in the mucosa. The uterine glands are larger and a greater number of them contain cellular debris in their lumine than in the previous uterus. The formation of the retention cysts is probably caused in the following manner: .Invo- lution of the uterine glands is very rapid, resulting in the accumulation of large quantities of cellular debris in the lumine of the glands. The remains of the de- stroyed cells are not absorbed in situ but are exfolia- ted into the lumine of the glands where they are either liquified by the enzymes cf the dead cells or are washed into the lumen of the uterus by the secretion from the glands. The cellular debris may occlude the orifices of the glands, stapping the flow of secretion and causing the formation of a retention cyst. Further evddencc that this is procable may be adduced from the fact that cellu- ~lar debris is found in the lumhmlof the cysts,(Fig.18,b). The area between the glands does not appear to con- tain as many connective tissue fibres as the previous uterus and the mucosa is loosely attached to the muscular wall. Histology of the Cotyledon Nearly all the crypts in the cotyledons contain por- tions bf chorionic villi which were retained at the time the chorion was passed. The cells of the villi are ne- 35 crosed as are all the cells in the crypt walls except at the fundus of the crypts next to the line of hyaline de- generation. The necrotic crypt mass is not protruding from.the summits of the cotyledons as described in the fourth day postpartum uterus. Soon after the foetal membranes were passed a por- tion of the chorion with chorionic villi on it was fixed in Bouin's solution. Fig. 19 is a photomicrograph of a section cut through the villi. All but a few of the cells of the villi are necrotic. Several large thrombosed blood vessels can be seen. Ewe 8040 Sixth Day Postpartum This ewe lambed on April 23, 1932 at 3:45 P.M. The foetal membranes were not recovered. She was killed at 10:00 1.M. on April 29, 1s32. The right horn is 470 millimeters in length and 60 millimeters at its greatest diameter. The left horn is 330 millimeters in length and 43 millimeters at its greatest diameter. There is no evidence of any retained foetal membranes in the lumen of the uterus showing that the membranes were passed but not found. The cotyledons are arranged in four parallel rows in the right horn but are scattered in the left horn. 36 Ninety-one cotyledons are present in the uterus. There is a small quantity of thick, sticky chocolate-brown exudate in the lumen of the uterus. Histology of the Glandular Area Vacuolar degeneration of the glandular epithelium is still going on. Rugac formations of the mucosa are not as numerous as in previous uteri, and the rugae are not as long. involution of the uterine glands is about complete. No vacuoler degeneration of gland cells could be found and cellular debris is found in the lumine of only a few of the glands. The area between the uterine glands appears to have less connective tissue than was found in the fourth day postpartum uterus, (Fig. 20, b). The mucosa does not ap- pear to be as firmly attached to the muscular wall as in the previous uterus. The edematous appearance of the glandular mucosa or relatively less dense appearance of the connective tissue gives one the impression that involutionary changes have not been as rapid in this uterus as in some of the pre- vious uteri. 37 Histology of the Cotyledons Nearly all of the cells in the decidual crypt mass are necrosed, (Fig. 20, a). A large number of crypts are still visible, due to the retention of a great many chorionic villi in the crypts, (Fig. 20, d). In Fig. 21, which is a higher magnification of a portion of a coty- ledon, the portions of retained chorionic villi are more distinct. In Fig. 21 the line of hyaline degeneration on the inner edge of the placental matrix cells is indica- ted at (b). There is no infiltration of leucocytes into the ne- crotic mass of the cotyledons or into the exfoliated cellular debris that constitutes part of the exudate in the lumen of the uterus. The lack of leucocytes is hard to understand in view of the fact that each cotyledon has a large mass of necrotic tissue consisting of the decidu- al crypt mess. There is no evidence that the necrotic crypt mass is being invaded by capillaries or fibroblasts from the pla- cental matrix cells that surround it. The necrotic crypt mass is evidently being liquified by autolysis and also reduced in volume by exfoliation in- to the lumen of the uterus. 38 Ewe 8034 Seventh Day Postpartum This ewe lambed on April 22, 1932 at 8:43 A.M. The foetal membranes were not recovered. She was killed on April 29, 1932 at 10:00 A.M. The right horn is 370 millimeters in length and 44 millimeters at its greatest diameter. The left horn is 280 millimeters in length and 33 millimeters at its greatest diameter. Upon opening the uterus no evidence of any retained membranes can be seen, showing that the membranes were passed but not found. Covering the glandular epithelium is a large quanti- ty of the characteristic sticky chocolate-brown exudate. One hundred and thirty-four cotyledons are present in the uterus. The cotyledons are arranged in four par- allel rows in each horn. In this uterus the decidual crypt mass of the cotyle- dons is projecting from the Openings on their summits as previously described in the fourth day postpartum.uterus. Hanging or projecting from a large number of cotyledons is what appears to be portions of the decidual crypt mass (F13. 23, 0) e Histology of the Glandular Mucosa Rugae of the surface of the glandular mucosa are not 39 nearly as numerous or long as in previous uteri, (Fig. 22, d). Vacuolar degeneration of epithelial cells is still in progress. involutionary changes in the uterine glands appear to be complete. Connective tissue fibres are rela- tively more abundant in the area between the glands. The mucosa has the appearance of being firmly attached to the muscular wall except directly under the cotyledons. The lumine of the blood vessels are being reduced or oblitera- ted by proliferation of the intime, (Fig. 22, h). Histology of the Cotyledon The cells of the decidual crypt mass, Fig. 22 (a), are completely necrosed down to the permanent placental matrix cells indicated by the brace at (b). Nearly all the crypts are collapsed and are visible only where a portion of a chorionic villus has been retained, (Fig. 22, i). The walls of the cotyledons which consist of glandular mucosa and the permanent placental matrix cells are being pulled down toward the bases of the cotyledons. Two purposes are accomplished by the pulling down of the walls of the cotyledon. First, the dediduel crypt mass is turned out into the lumen of the uterus, thereby ex- posing a larger surface for the exfoliation and lique~ faction of the necrosed cells. Second, placental matrix cells which spread out into a narrow band in the cotyle- 40 don of pregnancy are drawn into a caruncular mass in the mucosa. There is no evidence of leucocytic infiltration either into the necrotic crypt mass or into the exudate on the glandular mucosa. Eve 8026 Ninth Day Postpartum This ewe lambed on April 10, 1932 at 10:15 A.M. The foetal membranes were passed at 2:00 P.M. She was killed on April 19, 1932 at 2:15 P.M. The right.horn is 235 millimeters in length. Great- est diameter not taken. The left horn is 315 millimeters in length and 26 millimeters at its greatest diameter. The endometrial surface of the uterus is covered with a small quantity of the thick, sticky, chocolate- brown exudate. The exudate has a shiny, dry appearance. The cotyledons in the right horn are arranged in four par- allel rows. In the left horn the cotyledons are irregular- ly arranged or scattered. A total of 92 cotyledons are present in the uterus. The cup-like depression is not present on the summits of the cotyledons and the walls are not covered with glandu- lar mucosa as in previous uteri. The cotyledons do not project as far into the lumen of the uterus as in previous “tori e 41 Histology of Glandular mucosa Rugae on the epithelial surface of the glandular mu- cosa are rapidly disappearing, (Fig. 23, c). Vacuolar dc- generation of the epithelial cells is still in process. The uterine glands are completely involuted. The area be- tween the glands seems to cbntain more connective tissue and the mucosa appears to be firmly attached to the muscu- lar well even directly below the cotyledons, (Fig. 23). Histology of the Cotyledon The seventh day postpartum uterus was the first uterus in which all the cells in the crypt mass were' found necrotic. in this uterus and in the subsequent uteri of the series all of the cells in the crypt mass are found ne- crotic. The greatest change observed taking place in this uterus is the reduction or receding of the glandular muco- sal walls of the cotyledon and the drawing together of the permanent placental matrix cells at the base of the decid- ual crypt mass, (Fig. 23, b). Comparing Fig. 14, Fig. 22, and Fig. 23, which are photomicrographs of cotyledons from the fourth, seventh and ninth day postpartum uteri, the changes that take place are quite evident. In Fig. 14 the cotyledon projects into the lumen of 42 the uterus one to two centimeters. The walls of the cotyledon consist of glandular mucosa and placental ma- trix cells indicated at (a) and by the (brace b). In Fig. 22, the walls of the cotyledon have receded or have been reduced so that they project only a few milli- meters above the mucosa that forms the inter-cotyledo- nary area of the endometrium. In Fig. 23 the sides of the necrotic crypt mass (a) are not covered by glandu- lar mucosa. The mucosal walls and the band of perma- nent placental matrix cells that covered the sides of the necrotic crypt mass have receded or have been drawn down to its base indicated at (b). As a result of these changes the necrotic crypt mass is everted into. the lumen of the uterus. The necrotic decidual crypt mass is now in the ideal position for its disposal. The disposal or the ne- crotic crypt mass in the subsequent uteri of the series consists of its elimination by liquefaction and absorp- tion, or by its exfOliation and passing off in the lochia. Ewe 8032 Tenth Day Postpartum Uterus. This ewe lambed on April 9, 1932 at 11:45 A.M. The foetal membranes were passed at 4:00 P.M. She was kill- ed on April 19, 1932 at 2:00 P.m. 43 The right horn measures 250 millimeters in length and 27 millimeters at its greatest diameter. The left horn measures 200 millimeters in length and 22 millimeters at its greatest diameter. One hundred and thirty-seven cotyledons are present in the uterus. Some Of the caruncular areas at the horn tips had either not produced cotyledons during pregnancy or had completely involuted. The cotyledons are masses of thick, sticky chocolate- brown material, (Fig. 24, d). 'Covering the glandular mucosa and in the lumen of the cervix is what appears to be some of the same material that is found on the cotyledons except that it is more fluid in consistency, (Fig. 24, f). At the ovarian ends of each horn there are cotyledons that appear to be almost completely involuted, (Fig. 24, e). The small cotyledons at the horn tips apparently involute more quick- 1y than the larger cotyledons in the middle of the horns. The decidual crypt mass on.two of the cotyledons was grasp- ed with a thumb forceps and pulled Off, (Fig. 24, c). A moist, glistening white surface with a dark pigment ring circumscribing the caruncular area is found. Histology of the Glandular Area Rugae formations on the glandular epithelium are rapid- ly disappearing or being reduced in size. The uterine glands are completely involuted. The glandular mucosa is firmly attached to the muscular wall and appears to contain rela- 44 tively more connective tissue than the glandular mucosa in uteri in which the uterine glands were not completely involuted, (Fig. 25, a). Histology of the Cotyledon The involutionary changes in the cotyledons of this uterus do not differ materially from those described in the ninth day postpartum uterus. The necrotic decidual crypt mass is averted into the lumen of the uterus, (Fig. 25, a). The glandular mucosal walls of the cotyledon have receded and the per- manent placental matrix cells are gathering into a mass at the base of the necrotic crypt mass, (Fig. 25, b). The cotyledons are more pedunculated. The glandu- lar mucosa stOps at the edge Of the decidual crypt mass, (Fig. 25, 1). Ewe 8039 Eleventh Day Postpartum This ewe lambed on April 8, 1932 at 10:00 A.M. The foetal membranes were passed at 3:00 P.M. She was kill- ed on April 19, 1932 at 10:00 A.M. The right horn is 250 millimeters in length and 24 millimeters at its greatest diameter. The left horn is 280 millimeters in length and 28 millimeters at its greatest diameter. 43 One hundred ten cotyledons are present in the uterus. There are cup-like depressions on their summits and the walls are covered with epithelium up to the circular Open- ings, (Fig. 26, d", l About 100 c.c. of a thick, yellowish-white, tenacious exudate is in the middle of the left horn, (Fig. 26, d). Histology of the Glandular Mucosa. In some respects this uterus shows delayed involu- tionary progress while in Other respects it shows advan- ced changes. it is one of the three uteri of the series in which a heavy infiltration of leucocytes was found. Overlying the epithelium in the glandular mucosa is a layer of leucocytes, (Fig. 27, a). The epithelial sur- face of the mucosa is thrown up into numerous rugae. Vac- uolar degeneration is active in the epithelial cells of the glandular mucosa. The process must have been slow or dormant during the first part of the puerperium, other- wise the rugae on the surface would be much shorter and not so numerous, (Fig. 27, b). The uterine glands also show evidence of delayed involutionary progress in that the lumine of the glands are much larger than would be ex- pected in an eleventh day postpartum.uterus, (Fig. 27, c). Further evidence of delayed involution can be seen in the 46 edematous condition of the connective tissue between the glands and its loose attachment to the muscular wall, (Fig. 27, c). Histology of the Cotyledon The condition found in the cotyledons in this uterus is rather surprising in comparison with the cotyledons in the ninth and tenth day postpartum uteri. 1n the ninth and tenth day uteri we found the gland- ular mucosa and placental matrix band, that constitutes the wall of the cotyledon, receding toward the base of the cotyledon. As the wall recedes the decidual crypt mass is being turned outward toward the lumen of the uter- us. In this uterus we do not find the glandular wall or placental matrix band receding toward the base of the coty- ledon, (Fig. 28). The edematous condition of the glandu- lar mucosa and its loose attachment to the muscular wall probably accounts for the walls of the cotyledons not be- ing reduced as in previous uteri. The heavy infiltration of leucocytes has resulted in the rapid erosion of the de- cidual crypt mass and we find only a small amount on the inner edge of the matrix cells, (Fig. 28, c). The erosion and removal of the decidual crypt mass has resulted in the formation of a cavity formerly occupied by the crypt mass. It would appear that involutionary changes in the 47 cotyledons are further advanced in this uterus because of the rapid removal of the decidual crypt mass. We believe however, that the rapid removal or the decidual crypt mass is not the most important result to be considered in involution of the ewe's uterus. In our Opinion the most important result is the averting of the decidual crypt mass so that it is exfoliated and eroded into the lumen of the uterus in order to avoid the invasion of the necrotic crypt mess with fibroblasts and the formation of scar tis- 8119 e Ewe 8042 Twelfth Day Postpartum This ewe lambed on April 6, 1932 at 11:00.1.M. The foetal membranes were passed at 2:00 P.M. She was killed on April 18, 1932 at 10:00 A.M. The right horn is 215 millimeters in length and 27 millimeters at its greatest diameter. The left horn is 205 millimeters in length and 34 millimeters at its greatest diameter. The lumen of the uterus is completely filled with thick, sticky, chocolate-brown exudate except for a short distance at the lower and of each horn near the internal es of the cervix. The lumen of the cervix is also full of exudate which is more fluid than that in the horns. The cotyledons were not counted as it was impossible to 48 do so without disturbing the structural relationship of the necrotic tissue with the underlying mucosa and thus destroying the correct histological picture. Histology of Glandular mucosa Vacuolar degeneration of the glandular epithelium is very pronounced, (Fig. 29, b). The uterine glands ap- pear to be completely involuted. There appears to be a relatively greater abundance of connective tissue in the glandular mucosa in comparison with previous uteri in which the glands were not completely involuted. Some of the dark brown exudate overlyingthe glandu- lar mucosa is indicated at (a) in Fig. 29. Here and there in the exudate can be seen cellular debris, doubt- less exfoliated portions of the necrotic crypt mass. Histology of the Cotyledons Involutionary changes in the cotyledons have not pro- grassed very far beyond those described in the tenth day uterus. The principle difference is in the placental ma- trix cells which are drawing together in a smaller and thicker mass beneath the decidual crypt mass, (Fig. 30,b). 49 Ewe 8036 Thirteenth Day Postpartum This ewe lambed on April 6, 1932 at 7:00 A.M. The foetal membranes were passed at 11:45 A.M. She was kill- ed on April 19, 1932 at 9:30 A.M. The length of the right horn is 225 millimeters. Diameter not recorded. The left horn is 305 millimeters in length. Dism- ater not recorded. In the lumen of the uterus is a small quantity of thick, sticky, chocolate-brown exudate. The lumen of the cervix is full of the exudate in a much more fluid state than that in the horns. 0n the t0p of the cotyledons are flat, slightly oval discs of dark chocolate colored material which are very sticky to the touch. These flat, soft, sticky caps are very easily removed from the cotyledons, (Fig. 3l,d). There are 89 cotyledons in the uterus. Histology of Glandular Mucosa The glandular mucosa is in about the same state as described in the twelfth day uterus. Histology of the Cotyledons The cotyledons are in about the same stage of invo- to 30 lution as those in the twelfth day uterus except that there has been more of the decidual crypt mass eroded or exfolia- ted into the lumen of the uterus. Ewe 8028 Fourteenth Day Postpartum This ewe lambed on March 30, 1932 at 11:45 A.M. The foetal membranes were passed at 12:45 P .M. She was killed on April 13, 1932 at 10:30 A.M. The right horn is 150 millimeters in length and 21 millimeters at its greatest diameter. The left horn is 175 millimeters in length and 25 mil- limeters at its greatest diameter. There are 123 cotyledons present in this uterus. For about three-fourths the way up each horn from the internal es of the cervix the exudate is more fluid than in the horn tips, where it is the characteristic thick,chocolatc- brown exudate similar to that already described. In the lower part of each horn where the exudate is fluid there is not as much of the necrotic crypt mass on the summits of the cotyledons as in the upper parts of the horns where the exudate is thick and comparatively dry. Histology of the Glandular Mucosa The rugae projecting above the rest of the glandular 51 mucosa are covered with a peculiar type of epithelium which differs from the epithelium covering the lower, flatter portions of the mucosa, (Fig. 32, a). The epi- thelial cells on the rugae are much longer and the nu- clei are closer to the free ends of the cells, while the epithelium covering the flatter portions of the mucosa is composed of much shorter cells and the nuclei are near the base of the cells. Vacuolar degeneration is seen on- ly in the tall epithelial cell on the rugae. The lumine of the blood vessels are gradually being reduced by pro- liferation of the intima. Connective tissue fibres are found thickly scattered between the glands, (Fig. 32,c). Histology of the Cotyledons In the middle and cervical ends of the horns the cotyledons are nearly denuded of the necrotic decidual crypt masses, (Fig. 33, a). 0n cotyledons where the decidual crypt mass has been eroded down to the placen— tal matrix calls, epithelial cells from the glandular mucosa are beginning to grow over and cover the matrix cells, (Fig. 32, b). The placental matrix cells are grouping into the caruncular mass, (Fig. 33, b), simi- lar to that found in the nonpregnant uterus. 52 Ewe 8030 Sixteenth Day Postpartum This ewe lambed on April 5, 1932 at 1:45 P.M. The foetal membranes were not recovered. She was killed on April 21, 1932 at 10:15 A.M. The right horn is 265 millimeters in length and 20 millimeters at its greatest diameter. The left horn is 290 millimeters in length and 21 millimeters at its greatest diameter. There is no evidence, on Opening this uterus, of retained foetal membranes thus showing that they were passed though not recovered, (Fig. 34). involution of this uterus appears to be much slower than in the preceding uterus. The elimination of the de- cidual crypt mass from the cotyledons by liquefaction is much slower, (Fig. 34). Ninety-eight cotyledons are pres- ent in the uterus. The exudate in the lumen of the uter- us is of a thick, sticky chocolate-brown character and is not as fluid as that in the preceding uterus. Some of the exudate in a more fluid state than that in the horns can be seen in the lumen of the cervix, (Fig. 34, c). The decidual crypt mass of the cotyledons is easily re- moved by grasping it with a thumb forceps. Several were removed in this manner, (Fig. 34, d). 53 Histology of the Glandular mucosa The epithelial surface is much flatter than in any uterus yet examined, (Fig. 35, c). However, not all of the epithelial surface of the glandular mucosa is as free from rugae as shown in Fig. 35. Histology of the Cotyledons The cotyledons present the usual features with the necrotic crypt mass averted toward the lumen Of the uter- us, and the placental matrix cells drawing together at the base of the crypt mass, (Fig. 35, a and b). Ewe 8033 Seventeenth Day Postpartum This ewe lambed on April 4, 1932 at 2:45 P.M. The foetal membranes were passed at 5:00 P.M. She was killed on April 21, 1932. 1 The right horn is 160 millimeters in length and 18 millimeters at its greatest diameter. The left horn is 155 millimeters in length and 18 millimeters at itsgreatest diameter. Quite a contrast is found between the endometrial surface of this uterus and that found in previous uteri, (Fig. 36). The cotyledons have little or none of the 34 decidual crypt mass on their summits, (Fig. 36, d), and there is but a scanty amount of exudate in the lumen of the uterus. One hundred and twenty-five cotyledons are present in the uterus. The epithelium of the glandular mucosa is white in color and has a smooth glistening ap- pearance in contrast to the fluffy, wrinkled epithelium of the mucosa during the first part of the puerperium. Histology of the Glandular Mucosa The epithelium is relatively smooth with but few rugae formations on it, (Fig. 37, d). The mucosa is thicker and the areas between the glands are filled with connective tissue. The walls of the blood vessels are thick and their lumine are being slowly reduced in size. Histology of the Cotyledons The decidual crypt mass is eliminated almost down to the placental matrix cells. In Fig. 37 only a small amount is found at (a). The epithelium is spreading over the permanent matrix cells from the glandular muco- as. in Fig. 37 (a) can be seen how far the epithelium has spread over the matrix cells. The mass of matrix cells has contracted into the caruncular shape similar to that found in the non-pregnant UtGI‘UIe 35 Ewe 8045 Twenty-second Day Postpartum This ewe lambed on March 30, 1932 at 3:45 P.M. The foetal membranes were passed at 8:00 P.m. She was killed on April 21, 1932 at 10:00 A.M. The right horn is 190 millimeters in length and 24 millimeters at its greatest diameter. The left horn is 170 millimeters in length and 22 millimeters at its greatest diameter. involution is not yet complete as some of the coty- ledons, especially those in the right horn, appear to have some of the decidual crypt mass on their summits, (Fig. 38). There is only a small quantity of exudate in the uterus. One hundred cotyledons are present. Histology Of the Glandular Mucosa About the only change in the mucosa from that al- ready noted in the seventeenth day uterus is the smaller lumine of the blood vessels, (Fig. 39, a). Histology of the Cotyledons Nearly all Of the decidual crypt mass has been elimi- nated down to the caruncle or placental matrix cells, (Fig. 39, a). The caruncle is covered with epithelium.ex- cept where there is still a small portion of the decidual crypt mass to be eliminated. \J 56 Ewe 8031 Twenty-sixth Day Postpartum This ewe lambed on April 4, 1932 at 9:00 A.M. The foetal membranes were passed at 11:45 A.L'I. She was kill- ed on April 30, 1932 at 1:00 A.M. The right horn is 159 millimeters in length and 18 millimeters at its greatest diameter. The left horn is 185 millimeters in length and 12 millimeters at its greatest diameter. The endometrial surface of this uterus has about the same appearance as that of the twenty-second day uter— us. Some of the caruncular elevations have a ring of pig- ment around their edges. One hundred twelve cotyledons are present in the uterus. Histology of the Glandular Mucosa The glandular mucosa has the appearance of that in a non-pregnant uterus except that the blood vessels are not completely involuted. Histology of the cotyledons Involution of the cotyledons is nearly complete (Fig. 40). In Fig. 40 at (a) is a small amount Of decidual tis- sue yet to be eliminated. Nearly all of the placental matrix cells of the caruncles are covered with epithelium. 57 Ewe 8029 Thirtieth Day Postpartum This ewe lambed on April 2, 1932 at 8:00 A.M. The foetal.membranes were not passed. She was killed on May 2, 1932 at 10:00 A.M. The right horn is 215 millimeters in length and 17 millimeters at its greatest diameter. The left horn is 180 millimeters in length and 17 millimeters at its greatest diameter. In the lumen of the right horn is a large amount of solid, sticky chocolate-brown material which is undoubt- edly part of the foetal membrane that was retained, (Fig. 41, a). The left horn contains a small amount of choco- late—brown, fluid exudate. The general appearance of the andometrium.does not indicate that involution has been retarded because of the retained fcetal membranes. The caruncles have a bright, shiny appearance as if their sur- face is completely covered with epithelium. One hundred thirty-four cotyledons are present in the uterus. Histology of the Glandulariflucosa Except for the blood vessels, the glandular mucosa has completely involuted. Histology of the Cotyledons The cotyledons are completely involuted. All of the 58 decidual crypt mass has been eliminated from the placen- tal matrix cells and the latter are covered by epithe- lium, (Fig. 42). In Fig. 43 can be seen a section through the sticky chocolate-brown mass found in the right horn. It is com- posed of a mass of necrotic tissue undoubtedly a part of the foetal membrane. There is no av1dance of a heavy in- filtration of leucocytes in this uterus such as would be expected if the foetal membrane had been retained due to infection. Summary of Involution in the Mucosa of the Ewe's Uterus The involutionary changes in the mucosa Of the uteri of eighteen ewes have been traced from a few hours after parturition to thirty days postpartum. A brief de- scription was given of the non-pregnant and pregnant uterus. It was shown in the description of the pregnant uterus that great changes take place in the structural elements of the mucosa during gestation. There is a great increase in area or the mucosa dur- ing gestation. This increase in area calls for a great increase in numbers of epithelial cells that cover the mu- cosa because the epithelial cells in the non-pregnant and 53 pregnant uterus do not differ in size. The uterine glands also increase in size. The in- crease in size of the glands is accomplished by an in- crease in number of epithelial cells because there is no change in size of these cells in the non-pregnant and pregnant uterine glands. The increase in size of the lu- mine of the blood vessels is undoubtedly due to a prolif- eration of cells in their walls. With the increase in size of the uterine glands and blood vessels there appears to be a relative decrease in the connective tissue between these structures, and the mucosa seems to be very loosely attached to the muscularis. Compare (Fig. 2, a) with (Fig. 4, f). Greater and more striking changes take place in the caruncles after conception. After the epithelial cells are denuded over their surface the placental matrix calls of the caruncles are stimulated7ao proliferate great masses of new cells by the villiIETTtha choriéfik These new cell growths from the matrix cells form crypts that grow up around the elongating and branching villi of the chorion. ln addition to the formations of crypts from the matrix cells there occurs a rearrangement of the pla- cental matrix cells from the caruncular mass shown in (Fig. 2, c) to the band of cells surrounding the peri- phery of the crypts (Fig. 3, c). 60 After parturition the elimination of the structural elements in the mucosa that proliferated during gesta- tion, followed by repair, constitutes involution of the MHOOBO e involution of the Glandular Mucosa involution of the uterine glands was found to be a relatively rapid process in comparison with the changes in other parts of the mucosa. The excess epithelial cells of the gland are destroyed by vacuoler degenera- tion. The degenerated cells are not absorbed in situ but are exfoliated into the lumine of the glands. Proof of this was adduced from the fact that after the glands had involuted to the size of glands found in a non-pregnant uterus, vacuoler degeneration in the cells or the glands stOps and cellular debris is not found in their lumine. The mucosa of the uterus in Ewe 8027, fifth day postpartum, was found studded with numerous retention cysts (Fig. 17). The theory was advanced that the cysts were caused by the exfoliated cellular debris, in the lumine or the glands, occluding their orifices and stOpping the glandular secretion from flowing into the lumen of the uterus. The secretions than accumulated in the glands forming the retention cysts. The same type of vacuoler degeneration found in the 61 glands was found destroying the excess epithelial cells on the glandular mucosa, (Fig. 7, b) and (Fig. 29, b). The process in the epithelial cells of the mucosa was found in progress in all the uteri of the series. It cannot be stated whether the degenerated cells were ex- foliated into the lumen of the uterus or absorbed in situ, because of the large amounts of cellular debris in the exudate lying on the epithelium. No evidence of the cells being absorbed in situ was observed. Involution of the Cotyledons. After parturition and the passing of the foetal membranes the empty crypts of the cotyledon are left (Fig. 5, c) surrounded by the permanent placental ma- trix cells (Fig. 5, a). A portion of the glandular mu- cosa covers the walls of the cotyledon that project in- to the lumen of the uterus. The first involutionary change noted in the cotyle- don was a line of hyaline degeneration involving the periphery of the crypts on the inner edge of the placen- tal matrix band (Fig. 5, d). Some of the placental ma- trix cells may be involved, although the line of hyaline degeneration does not extend any deeper than the fundus of the crypts that contain necrotic tips of retained chorionic villdq (Fig. 9, brace b), (Fig. 10, b) and 62 (Fig. 13, brace b). The line of hyaline degenerated cells (d) forms a complete barrier between the outer circumfer- ence of the crypt mass (a) and placental matrix band (Fig. 5, a). We are not able to state what causes the formation of this line of hyaline degeneration but believe that some very important changes occur as a sequence of its for- metion. It was observed that the blood vessels that traverse the line of hyaline degeneration from the matrix band to the crypts were thrombosed in both these areas. Proof that the blood vessels are thrombosed is based on the macroscOpical observation that the crypt mass in the cotyledons is~ anemic in appearance during the first three or four days of the puerperium, after whdphthay be- come brown in color, due to degenerative changes of the cells. Histological examination of the cotyledons in the first, second and fourth day postpartum uteri reveals more convincing eVidence. It is hard to conceive that the vil- lus could be expelled from the crypts during the passing of the foetal membranes without rupturing some of the capillaries and smaller blood vessels in the crypt walls causing hemorrhages. In no case, however, was there any evidence of hemorrhages from the maternal blood vessels in the crypts. This evidence, coupled with the coagu- 63 lated or agglutinated appearance of the blood in the vessels is convincing proof that the blood vessels are thrombosed. The final proof, however, was found in the cotyledons of Ewe 8043, fourth day postpartum. This uterus was one in which a heavy infiltration of leucocytes was found. The leucocytes were found invad- ing the crypt mass from the blood vessels in the pla- cental matrix band (Fig. 14, brace d). All parts of the crypt mass would have been invaded by leucocytes from the blood vessels that traverse its whole extent if they had not been thrombosed. We are not prepared to state whether the hyaline degeneration causes the thrombosing of the blood ves- sels, or whether it is due to some other cause. As a sequent of the blood vessels being thrombosed the cells of the crypt mass are deprived of nutrition and necrose. The cells at the apex of the crypts far- thest away from the placental matrix band necrosc first. Necrosis of the cells in the crypts progresses very rapidly from their apex towards the fundus of the crypts. In the third day postpartum uterus nearly all the cells in the crypt mass are necrosed except some of the cells in the fundus of the crypts. It was not until the seventh day postpartum uterus was examined, however, that all the cells in the crypt mass were 64 found to be necrosed. The Close proximity of the cells in the fundus of the crypts to the blood vessels in the placental matrix band, from which they may have derived nourishment, may eXplain their delayed necrosis, The beginning of a new involutionary process was Observed in the cotyledons of the seventh day postpar- tum uterus. This procass consists of the drawing down or receding of the glandular mucosa and placental ma- trix band that constitutes the wall of the cotyledon surrounding the necrotic crypt mass. The receding of these structures is the reverse of that which took place during the development of the cotyledons of preg- nancy (see description of ”Pregnant Utari”). The changes that take place in the cotyledons as a result of the process are very clearly illustrated in figs. 20, 22, and 23 which are photomicrographs of coty- ledons from the sixth, seventh, and ninth day postpartum uteri. In (Fig. 23) the glandular mucosal wall has been drawn down or has receded, and the placental matrix band which appears as a thin band of calls around the peri- phery of the necrotic crypt mess in (Fig. 20, c) has re- ceded or has been drawn down into a thickened mass be- low the necrotic crypt mass (Fig. 23, b). As the puer- perium advances the necrotic crypt mass (Fig. 23, a) is eroded, due to autolysis. or in part is exfoliated into 65 the lumen of the uterus where it is liquefied. Some of the exfoliated necrotic crypt mass may even pass through the cervix into the vagina (Fig. 24, f) and (Fig. 34, e). That part of the necrotic crypt mass which passes through the cervix into the vagina is evidently lique- fied before reaching the vulva as there was no external evidence of a uterine discharge after the first two or three days of the puerperium. We have no explanation to Offer that would account for the drawing down or receding of the cotyledonary walls that surround the necrotic crypt mass. From the ninth day onward the necrotic crypt mass becomes smaller and smaller due to liquefaction and ex- foliation. Compare (Fig. 23, a) with (Fig. 33, a). During this time the uterus is constantly becoming small- er, which may account for the placental matrix cells be- ing formed into a caruncular shaped mass below the ne- crotic crypt tissue. Compare (Figs. 25, b and 37, b. The uterine epithelium from the inter-cotyledonary glandular mucosa begins to spread in over the placental matrix cells as the necrotic crypt mass is denuded from its surface (Fig. 37, e). ’In (Fig. 42) a photomicro- graph of a cotyledon of the thirtieth day postpartum uterus all of the necrotic crypt mass has been eroded from the placental matrix mass and the surface of the 66 matrix cells is completely covered with epithelium. Involution of the cotyledon of pregnancy is now complete and it is restored to the caruncular shaped mass of placental matrix cells found in the non-preg- nant uterus. Compare (Figs. 1 and 41) and (Figs. 2 and.4z). The disposal of the large amounts of necrotic tis- sue fromrthe cotyledons during the puerperium is a non- inflammatory process. Proof of this statement can be adduced from the fact that only three of the series of eighteen uteri showed a heavy infiltration of leuco- cytes. The heaviest infiltration of leucocytes was found in the eleventh day postpartum uterus. There was also a heavy infiltration of leucocytes in the fourth and twelfth and a slight infiltration in the thirteenth day postpartum uterus. In the other uteri of the series leucocytes were lacking or were present in scan- ty numbers. The presence of large number of leucocytes un- doubtedly denotes infection or inflammatory processes other than the normal processes of involution. The foetal membranes were recovered from all but five ewes of the series. See (Table 111). in the uter- us of only one of the five ewes from which the foetal membranes were not recovered was any evidence found 67 that the membranes had been retained in the uterus. The uterus from which the foetal membranes were not passed was from ewe 8029 thirty days postpartum. The right horn of the uterus contained a mass of necrotic tissue, sections of which showed it to be a portion of the re- tained foetal membranes (Figs. 41 and 43). There was no evidence of leucocytic infiltration in the mucosa of this uterus showing that the membranes must have been retained due to some other cause then in- fection or inflammation. in examining the foetal membranes passed after par- turition, a quantity of thick, white gelatinous sub- stance, about the size of a small apple, was found ad- hering to the uterine surface of the membranes at the horn tips opposite to the Opening of the oviducts. The substance had about the same appearance as the uterine seal in the cervix, and would indicate that the ori- fices of the oviducts are sealed during pregnancy in much the same way that the cervix is sealed. Three tables are included in this paper.- In Table I are tabulated the measurements of the uterine horns. Variations in length and diameter are evident, but in general there is a gradual decrease in size as the puerperium advances. The length of the right horn of the uterus of awe 8029 thirtieth dey postpartum is 68 greater than any of the horns of the preceding uteri go- ing back to the seventeenth day poatpartmm uterus. The length of the right horn of the uterus of ewe 8029 is undoubtedly due to the retained foetal membranes found in the horn. The retained foetal membranes did not ap- pear to retard involution of the uterus in any other re- spect as the mucosa was completely regenerated. In Table II are tabulated the time at which partu- rition took place, and the interval in hours between parturition and the passing of the foetal membranes. The average time for the twelve foetal membranes recovered was 3 hours and 35 minutes. In Table III are tabulated for comparison the num- ber of foetal placental areas on the chorion, and the number of cotyledons or raised areas on the endometrial surface of the uterus, from which the foetal membranes passed. It is quite evident from the comparisons that the foetal membranes do not always make contact with all the caruncles in the uterus. in fact the number of foe- tal placentae on the foetal membranes was less in all cases except in awe 8027 where the foetal membranes did 'u; make contact with all the caruncles present in the uterus. in the other uteri of the series the compari- son of the foetal placantae on the membranes was less than the number of cotyledons and non-functioning carun- cles in the mucosa of the uterus from which the foetal 69 L4! membranes passed. This is in accord with Hammond's (12) findings in the cow and is further evidence that the pow— er of initiating placental growths on the caruncles rests with the chorion. TABLE I Length of Number Date Date Ewes Greatest Length of Greatest Number of of Ewes were Right Horn Diameter Left Horn Diameter Days Post Ewe Lambed Killed in M.M. Right Horn in M.M. Left Horn partum Ewes were Killed 24 1-26-52 1-26-52 Approxi- mately 12 hours 8044 5-7-52 5-9-52 590 68 500 47 2nd Day 8055 5-6-52 5-9-52 560 65 290 50 5rd " 8045 5-5-52, 5-7-52 420 54 500 65 4th " 8027 4-25-52 4-50-52 550 60 490 76 5th " 8040 4-25-52 4-29-52 470 60 550 45 6th " 8054 4-22-52 4-29-52 570 44 280 55 7th " 8026 4-10-52 4-19-52 255 515 26 9th " 8052 4-9-32 4-19-52 250 27 200 22 10th " ' 8059 4-8-52 4-19-52 250 24 280 28 11th " 8042 4-6-52 4-18-52 215 27 205 54 12th " 8056 4-6-52 4-19-52 225 505 15th " 8028 5-50-52 4-15-52 150 21 175 25 14th " 8050 4-5-52 4-21-52 265 20 290 21 16th " 8055 4-4-52 4-21-52 160 18 155 18 17th " 8045 5-50-52 4-21-52 190 24 170 22 22nd " 8051 4-4-32 4-30-32 159 18 185 12 26th a» 8029 4-2-52 5-2-52 215 17 180 17 50th " ThBLE II. not recovered umber Time Lwes Time foetal mem- Interval in Hours Between Eof Lambed branes were passed Dropping of Lamb and Pass- we ing of the~Foeta1 Mem- branes 24 Between 11:00 P.M. & 7:'A.M Time not known 8044 11:50 atM. Foetal membranes not recovered 8035 1:00 P.M. 4:50 P.M 5 hours, 50 minutes 8045 9:50 A.M. 2:00 P.M. 4 hours, 50 " 8087 5:45 P.M. 6:45 P.N. 5 " 8040 5:45 P.M. Foetal membranes not recovered 8054 8:45 A.M. Foetal membranes not recovered 8026 10:15 A.M. 2:00 P.M. 5 " 45 " 3032 11:45 A.M. 4:00 P.M. 4 " 15 " 8039 10:00 A.M. 5:00 P.M. 5 " 8048 11:00 A.M. 2:00 P.M. 5 ” 8036 7:00 A.M. 11:45 A.M. 4 " 45 w 8086 11:45 A.M. 12:45 P.M. 1 " 53030 1:45 P.M. Foetal membranes ' . not recovered 2:45 P.M. 5:00 P.M. 2 " 15 " 3:45 P eMe 8:00 P.M. 4 n 15 ” 9:00 A.M. 11:45 A.M. 2 " 45 " 8:00 A.M. Foetal membranes TABLE III Comparison of the number of cotyledons and caruncles found in the involuting uterus with the number of foetal placentae found on the foetal membranes. Note- It is quite evident'from a comparison of the number of foetal placentae on the foetal membranes with the number of cotyledons and caruncles in the uterus that the caruncles in the non-pregnant uterus are potential cotyledons only and that these may or may not function during subsequent pregnancies. Number Number of Number of of Cotyledons foetal pla- Ewe and Non- centae on functioning chorion Remarks caruncles in uterus 24 No Count No Count Made Me de 8044 . 82 Foetal membranes not recovered 8055 86 81 I 8045 84 75 8027 85 85 8040 91 Foetal membranes not recovered 8054 154 ' Foetal membranes not recovered 8026' - 92 ' 85 8052 157 ’ 78 8059 110 64 8042 78 Uterus was filled with a thick exudate which was not disturbed to count cotyledons. 8056 89 Foetal membranes so badly torn no count was made. 8028 125 77 8030 98 Foetal membranes not recovered 8055 125 94 8045 100 48. One horn of the foetal membranes was - only half the length of the other. 8051 112 95 8029 154 Foetal membranes not recovered. 5. 6. 7. 10. ll. 12. 13. BIBLIOGRAPHY Friedlgnder, Utersuchungen uber den uterus. Liepzig 1870. hundrat und Engelman, Utersuchungen uber die uterus - schleimhaut in den wiener mediz. L ehrbuchem 1875. Leopold, Studium uber die uterus - mucosa, USW. arch. f. Gynoec und geburtsh. Bd. XII. Williams, J. Whitridge, Regeneration of the Uterine Mucose after Delivery, with Especial Reference to the Placental Site. Amer. Jour. of 0 bat. and Gyne. Nov. 1931, VOle XXII NOe 5, pp 66l-696e Fleming, Geo., Veterinary Obstetrics Ed. 2 revised. W. R. Jenkins, Publisher 1900. DeBruin, M. 0., Bovine Obstetrics. Translated by Wyman. W.E.A. 1901. Hilty, Heinrich, Utersuchungen uber die Evolution und, Involution der uterusmucosa Vom Rind, Schweig, Archiv. f. Tiekeilkunde, 1908. Hellman, E. T., Further Studies in the Disease of the Reproductive Organs of Cattle. Cornell Veterinarian, July, 1924. Williams, W. L., The Significance of Utero - chorion- ic lesions in the cow. Cornell Veterinarian, 19, 254, 1929. Marshall, Phil, Trans. Roy, Soc. B, 196, 1905. Casada, L. E. and McKenzie, F. F., The Oestrous Cycle of the Ewe; Histology of the Genital Tract. Research Bulletin 170, College of Agriculture, University of Missouri e hammond, John. The Physiology of Reproduction in the Cow. 1927. Assheton, R. The Morphology of the Ungulate Placenta, particularly the Development of that Organ in the Sheep, and notes upon the Placenta of the Elephant and Hyrax. Phil. Trans. Roy, Soc. B 198, 1906. Fig. 1 Non-Pregnant‘Uterue (A) Right horn, (b) left horn, (c) cervix, (d) vagina, (e) caruncles, (f) glandular mucosa. Fig. 2 Fig. 2 I 28 Caruncle and Glandular Mucosa Non-Pregnant Uterus. it and b) points at which glandular mucosa Joins the stroma of the caruncle, (c) matrix of the caruncle, (d) muscular wall of uterus, (e) glandular mucosa, (f) blood vessel in muscular layer of uterus, (g) uterine glands, (h) epithelium over glandu- lar mucosa. ,. A l 1 i r 0" Va /\‘ ‘ I " f. sa.-s! Fig. 5 Cotyledon fromhrregnant Uterus Fig. 5, I 12 (A ) (0) (c) permanent placental (d) muscular wall of uterus, (f) point at which glandular mucosa is attached a1 portion of chorion where villi enter crypt , to matrix, (5) short mucosal stem of cotyledon. ) chorion over glandular mucosa of uterus, (brace b) decidual.crypts of cotyledon, matrix cells of cotyledon, A n uterine glands, (A. A foetal plsge Fig. 4, X 78 Glandular'uucosa Pregnant Uterus. (A) chorion, (b) epithelium of chorion, (c) epithelium on glandular mucosa, (d) thin layer of dense connective tissue, (e) epithelium of glands, (f) louse connective tissue of mucosa, (g) muscular wall. Fig. 5, 1.8 Cotyledon of approximately 12 hours rest-partum. (A k b) placental matrix band, (c) decidual crypt mass, (d) line of hyaline degeneration, (a) muscular well of uterus, (f) serous coat, (g) uterine glands, (h) epithelium of glandular area. Fig. 6. Endometrium of 2nd. Day Postpartum Uterus. (A) cervix, (b) right horn, (c) left horn, (d) glandular mucosa, (e) cotyledon, (f) chocolate brown exudate on mucosa. .05 ...r .4 .W -. .. . . .Jfi . ..: .. . . sis .091st .e . 94.3.11: «Wynn. . . . la 7‘“. a a h. .. .. .10.» . ,. . . e , . ... , a l . l..l a... — Glandular mucosa 2nd day Post-partum Fig. 7, x 56. (d) connec- (b) vacuole degeneration of epithelial cell, (c) uterine gland with cellular debris in lumen, (A) epithelium, tive tissue. Fig. 8, I 10. Cotyledon 2nd. day.Post-partume (A) decidual crypt mass, (b) placental matrix band, (0) line of hyaline degeneration, (d) epithelium of glandu- lar mucosa, (a) muscular wall, (f) thrombosed blood vessel in crypt mess, (g) uterine glands, (h) blood vessel. Portion of Cotyledon 2nd. day Post-partum. Fig. 9, I 186. (d) tips of (a) blood vessel. (A) placental matrix cells, (b) line of hyaline degenera- tion, (c) walls of crypts with degenerating cells, a retained chorionic villus, Fig. 10, x 570. Higher magnification of Fig. 8. (A) placental matrix cells, (b) line of hyaline degenera- tion, (0) necrotic crypt cells, (d) tip of chorionic villus. {"2 04/ x57r Fig. 11. Endometrium of 5d. Day Postpartum‘Uterus. (A) cervix, (b) right horn, (c) left horn, (d) glandular mucosa, (e) cotyledon. Fig. 12, X 56. Rugae Formation on Mucosa 5rd. Day Uterus. (A) epithelium, (b) shallow layer of dense connective tissue, (c) uterine glands with lumen full of cellular debris, (d) blood vessels in process of involution (note thickening of intima), (e) connective tissue of loose glandular mucosa (note the few nuclei), (f) muscular wall. n . .. , . ‘ “v.7. \\ . .. . . 1.. fs .1 £4 c.>~\5\‘.. r; 1 . . .W 4 .. - p‘l— ‘1‘ . .“ e a .v w ‘1 .n a . . r .. Portion of Cotyledon 5rd. day Post-partum. Fig. 15, X 250. (b) line of hyaline degenera- (c) necrotic cells of crypt walls, (d) necrotic tip of (A) placental matrix cells, chorionic villus. tion, Fig. 14, X 15. Cotyledon 4th. Day Postpartum Uterus. (A) decidual crypt mass, (brace at b & c) placental matrix band, (brace at d) dark area around periphery of crypt mass being invaded by leucocytes, (a) epithelium over glandular mucosa covering wall of cotyledon, (f) uterine glands, (g) tip of chorionic villus retained in crypt, (h) thrombosed blood vessels in crypt mass. Fig. 15, I 225. Portion of Cotyledon 4th. Day Postpartum, (A) placental matrix cells, (b) crypt cells in process of mmrosis, (0) portions of chorionic villi, (d) leucocytes invading MTpt mass from placental matrix band. .o. .94.“ . . .6\ ...}...L. 1 . ash! 1‘ . . ~ . t‘ . . a finals}: ( Ur... .. . . - \ . D» .e. . 11...“. 1.... .lxvrmnfl. Gar. ... u ... . (\ _ II. ...»: .. ...; \3 .1. .9... .a. . 4 . , . ...- 4ng. . .. . . .. . ... .1 . ....x. .4 - ... ... . .. .. .-. . .. fr. , , . .. ...: unaware. .. n... ....u.u I . I . a . I J. A ... . ... ) ... 5‘ aisle-4?... . D; -..L\.hw.r/o}I-,,.4xe..r. ..,.. .. e . ..a .... , Fig. 15. 14y 92-7. 04)! Fig. 16, I ll. Cotyledon With nest of Decidual Crypt Mass Removed Before Fixing in Bouin's Solution. (A) cavity from which crypt mass was removed, (b, b & c) placental matrix band,(d) exudate of cellular debris, (d) epithe- lium of glandular mucosa, (f) uterine glands, (g) blood vessels, (h) muscular well, (1) portions of crypt mass not grasped by thumb forceps and therefore not removed. 47 ' .10 {Win-- ‘ . 03027. 5 DAYS Russ? Home Fig. 17. Endometrium of 5th. day Post-partum.Uterus. (A) retention cysts, (b) cotyledon, (c) exudate. Fig. 18, I 22. Retention cysts in Glandular Iucesa. (A) retention cysts, (b) cellular debris in lumen of cyst? (a) uterine gland with cellular debris in lumen, (d) uterine gland with large lumen, (a) muscular wall of uterus. )/ (Vilhfi‘ ’,*.a 4.3“ l ... Fig. 19, X 75. Foetal Placenta of 5th. Day Postpartun.0horion. (A) necrotic cells of foetal villi, (b) red blood cells, (c) blood vessel. «Info/1.} ’ [bf Cotyledon 6th Day Postpartum. Fig. 20, I 12-1/2. (A) decidual crypt mass, (b) glandular mucosa with but few connective tissue cells, (0) placental matrix cells, (d) portions of chorionic villi retained in crypts, (e) epithelium of glandular mucosa, (f) muscular wall of uterus. Fig. 21, X 150. Portion of Cotyledon 6th. day Post-partum. (A) placental matrix cells, (b) line of hyaline degenera- tion, (0) portion of chorionic villus in crypt, (d) thrombosed blood vessel in crypt wall. .‘ir ‘ Tar-.- ' W)” ‘3‘..- ”flying/egg: ‘V"" W.?’$fifi; W?! J“ {31%- ‘wififlg' ‘ ' . 1" (a! ..- ‘ r~° v- . a Fig. 22, x 12-1/2. ' Cotyledon of 0th Day Postpartum.Uterus. (A) decidual crypt mass, phery of crypt mass, 9 (0) Peri- (d) epithelium of glandular mucosa, foliated crypt cells in exudate, (b) placental matrix band (a) ex- (f) uterine glands, (g) muscular wall of uterus, (h) lume of blood vessels being reduced by pro- liferation of intima, (i) portion of chorionic villus in crypt. Fig. 25, 1'12-1/2. Cotyledon 9th. day Post-partum Uterus. (A) decidual crypt mass, (b) placental matrix cells, (c) epi- thelium of glandular mucosa, (d) dense connective tissue under epithelium, (e) uterine glands, (f) portion of chorionic villus, (g) muscular wall, (h) blood vessels. Fig. 25, x 12-1/2. Cotyledon 10th. Day Postpartum Uterus. (A) decidual crypt mass, (5) placental matrix cells, (c) epithe- lium.of glandular mucosa, (d) uterine glands, (f) muscular wall, (3) blood vessels, (h) portions of chorionic villus, (1) point at which the glandular epithelium.circumscribed opening into cotyledon. Fig. 26. (A) right horn, (b) left horn, (a) thick white exudate. (c) cervix, Endometrium 11th. Day Postpartum Uterus. (d) cotyledon, Fig. 27, x 26. Glandular mucosa 11th. Day Postpartum. (A) Leucocytes on epithelium, (b) epithelium, (c) uterine glands, (d) blood vessel, (e) connective tissue of mucosa, (f) muscular wall of uterus. Fig. 28, I 20. Cotyledon 11th. Day Postpartum. (A) placental matrix cells, (b) leucocytes, (c) light area from.which the decidual crypt mass has been denuded, (d) epithelium over glandular mucosa, (e) uterine glands, (f) blood vessel, (g) connective tissue of glandular mucosa. \I .d'Juila... fa N Fig. 29, I 56. Glandular mucosa 12th day Post-partum. (A) exudate overlying epithelium, (b) epithelial cells in process of vacuoler degeneration, (c) connective tissue of glandular mucosa, (d) muscular wall, (a) uterine glands, (f) blood vessel. .\ LI". ,. U ‘I ‘ ,1 .‘I-i 1': . '-I I ., 3,2..‘__.| _. keafi -. ' w"-.. ‘ gv-K Fig. 50, X 10. Cotyledon 12th. Day Postpartum. (A) decidual crypt mass, (b) placental matrix cells, (c) epithelium over glandular mucosa, (d) muscular wall of uterus, (e) blood vessels in loose connective tissue of mucosa under placental matrix cells, (f) uterine glands. Fig. 51. Endometrium 15th. Day Postpartum Uterus. (A) right horn, (b) left horn, (c) cotyledon, (d) cotyledon from which the decidual crypt mass was removed. J';. '-\ L." . ‘ V . fi.‘ ‘ . U. a ., ~\~ ‘ ‘ . I \ a.\‘ w’l a Z ‘ a '. .’ ‘ . . . - I" i I l “I"! '1 - I r . --- -1 ,_ .1, _MW 1. Fig. 52, X 56. Glandular Mucosa 14th. Day Postpartume (A) epithelium, (b) epithelium beginning to spread over placen- tal matrix cells, (c) connective tissue of mucosa, (d) muscular wall of uterus, (e) exudate overlying mucosa, (f) blood vessel, (g) placental matrix cells. .4 . . ‘ J. a -. -\ , \ a“. 7‘: -" _ . . .‘ v » ' "‘ 7'7‘3 l ,( - '. \ .‘.;" )i-‘lavf 4‘." --1 , . ix" 1 .\C‘>-’-’ ‘\ 3,ng -- 9' 7 -’ _’ Fig. 55, I 16. Cotyledon 14th. Day Postpartum. (A) decidual crypt mass, (b) placental matrix cells, (c) epithelium of glandular mucosa, (d) muscular wall of uterus, (a) blood vessels, (f) epithelium spreading over matrix cells, (g) exudate lying on mucosa. , _v._____ri _— 5030 /6 DA v5 Eig. 34. Endometrium 16th. day rost-partum Uterus. (A) right horn, (b) left horn, (c) cotyledon, (d) cotyledon from which decidual crypt mass was removed, (e) lochis in lumen of cervix. h. .. .’.‘__' .Vg‘.‘ {an _r . . , ' 1' t_\‘ ' ,“ A " z ‘ . I ‘-_ . " ~ '1 . '0: - -_ A a ( ‘jzr'J—‘g IN,“ :3 .'e.:§"" i. ..2 iv- 1‘ ' ' .\‘u .' y - ' . ‘1‘. . '. ' " . ' .. ' ~ ' " \t\ "3:1 'l-J» Q'Jl‘. J. ' \‘yfiwfi'lf.¥k~ 3" ( ".IT' ' o. 8'; .I "V" I ‘3" l; . v.1‘.- ..‘. ....'. ‘ \ O v 5:. I. 0"- I'..' I. q I ', a . ‘ v M... 4,5 r13. 35, x 32. ‘ Cotyledon 16th. Day Postpartum. (A) decidual crypt mass, (b) placental matrix cells, (c) epithelium on glandular mucosa, (d) muscular wall or uterus, (e) portion of retained chorionic villus. Fig. 36. Endometrium 17th. Day Postpartum Uterus. (A) right horn, (b) left horn, (c) cervix, (d) cotyledon. Fig. 37, X 26. cotyledon 17th. Day Postpartumt (A) small amount of decidual tissue, (b) placental matrix cells, (0) muscular walls, (d) epithelium on glandular mucosa, (e) epithelium spreading in and-covering placental matrix cells. -\ r‘ r- H943 v £2 DAYS Fig. 38. Endometrium 22nd. Day Postpartum Uterus. (A) right horn, (b) left horn, (c) cervix, (d) cotyledon. Fig. 39, X 26. Cotyledon 22nd. Day Postpartum. (A) small amount of decidual tissue, (b) placental matrix cells, (c) epithelium over glandular mucosa, (d) muscular wall of uterus, (a) blood vessels. Day Postpartum. Cotyledon 26th. 40, X 28. Fig. (e) epithe- (d) blood vessels, lium over glandular mucosa, (f) epithelium spreading over matrix 06118 e (A) small amount of decidual tissue, (b) placental matrix (0) muscular wall or uterus, cells, Fig. 41. Endometrium 30th. Day Postpartum'Uterus. (A) right horn, (b) left born, (c) cervix, (d) cotyledon, (e) retained foetal membranes. ,v .. ..Hw4._¢:.r. rick , . b ii It's... o,\SK Cotyledon 30th. Day Postpartum. 42, X 28. Fig. (c) muscu- (e) uterine (b) placental matrix cells (caruncle), (A) placental matrix cells completely covered with (d) epithelium on glandular mucosa, l 6 S S 6 V O l b m f lax wll : 688 m...“ .lr.a P81 616 Fig. 45, x 350. Retained Foetal Membranes 30th Day Postpartum Uterus. (A) probably a chorionic villus, (b) necrotic cells. ACKNOWLEDGEMENT I wish to acknowledge my indebtedness to Dr. E. T. Hellman, Professor of Animal Pathology, who made the investigation possible and who has willingly throughout the course of the investigation given me the benefit of his advice and wide experience. Andrew Waldmere Uren