MOLECULAR CONTRIBUTIONS OF NOTCH AND HIPPO SIGNALING TO ENDOMETRIAL STROMAL CELL DECIDUALIZATION
Endometrial stromal cell decidualization is required for pregnancy success and defects in this process are associated with infertility. Many of the intricate molecular mechanisms contributing to decidualization remain undefined. Two pathways implicated in endometrial stromal cell decidualization in humans in vitro, are the NOTCH and HIPPO signaling pathways. Previously conducted studies showed that NOTCH1, its transcriptional effector, RBPJ, and the effectors of the HIPPO signaling pathway, YAP1 and WWTR1, are required for decidualization initiation. To investigate the in vivo contributions of NOTCH and HIPPO signaling in decidualization, we generated genetically engineered mouse models with conditional deletion of Rbpj and Yap1 and Wwtr1. Decidual Rbpj deletion did not significantly affect female fertility supporting that NOTCH signaling activation is required for the initiation of decidualization but not its maintenance. However, conditional deletion of Yap1 and Wwtr1 in the female reproductive tract resulted in subfertility, a compromised decidualization response, partial interruption in embryo transport, blunted endometrial receptivity, delayed implantation and delayed subsequent embryonic development. Transcriptome analysis revealed aberrant maternal remodeling at 7.5 days post coitus and enrichment for terms associated with fertility compromising diseases like pre-eclampsia and endometriosis. Our results indicate that Yap1 and Wwtr1 are required for pregnancy establishment, decidualization initiation and maintenance, and pregnancy maintenance. These studies have implications for women’s health and support the continued investigation into molecular mechanisms contributing to female fertility.
Read
- In Collections
-
Electronic Theses & Dissertations
- Copyright Status
- Attribution-NonCommercial-NoDerivatives 4.0 International
- Material Type
-
Theses
- Authors
-
Moldovan, Genna Elisabeth
- Thesis Advisors
-
Fazleabas, Asgerally T.
- Committee Members
-
Jeong, Jae-Wook
Gallo, Kathleen
Chandler, Ronald
Ralston, Amy
- Date Published
-
2024
- Subjects
-
Cytology
Molecular biology
- Program of Study
-
Cell and Molecular Biology - Doctor of Philosophy
- Degree Level
-
Doctoral
- Language
-
English
- Pages
- 119 pages
- Permalink
- https://doi.org/doi:10.25335/jx3p-w675