Adverse experiences that occur early in life, known as early-life adversity (ELA), include factors such as the loss of a parent, exposure to violence, malnutrition, and infections; can disrupt normal developmental processes and significantly increase the risk of diseases later in life. Biological sex is another factor influencing disease risk, with evidence indicating that males and females react differently to ELA. Notably, females tend to be more vulnerable to the adverse long-term effects of ELA. In previous studies conducted by our group, early-weaning stress in pigs—a model for ELA—was linked to a hyperactive enteric nervous system, compromised intestinal barrier function, functional diarrhea, and chronic low-grade intestinal inflammation later in life. These effects were much more pronounced in female pigs compared to castrated male pigs. Still, the exact molecular mechanisms associated with this sexual dimorphism are still not well elucidated. Therefore, the objectives of the present study were to compare how female, male, and castrated male pigs weaned at either 15 days (early weaning condition) or 28 days (late weaning condition) respond to a lipopolysaccharide (LPS) challenge later in life (70-day-old), by evaluating the transcriptome of the ileum mucosa. By comparing samples from female and male pigs, we want to assess the effect of biological sex on the immune response, and by comparing male and castrated male pigs, we want to evaluate how castration status impacts the immune response.
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