Clinical PhD Student Cincinnati Children's Hospital and Medical Center Cincinnati, Ohio, United States
Abstract: Pregnancy and lactation demand significant energetic and metabolic resources, requiring maternal systems to undergo rapid adaptations comparable to those of high-endurance athletes. The small intestine plays a pivotal role in this process by increasing its absorptive capacity to support maternal metabolism and fetal development with an additional 500–800 kcal daily. These dynamic changes are influenced by key pregnancy hormones—human chorionic gonadotropin (hCG), progesterone, and estradiol (E2)—which drive essential biological functions. Intestinal growth factors, such as Epidermal Growth Factor (EGF), R-Spondin, WNT-3a, and Noggin, regulate the proliferation and health of intestinal epithelial stem cells, providing optimal conditions for the development of enteroids or “miniguts.”
EGF is critical for supporting organoid cell proliferation and growth. However, pregnancy hormones interact with overlapping pathways that modulate cellular behaviors in the presence or absence of EGF. For instance, progesterone promotes cell proliferation through the WNT pathway in certain mammalian cells while inhibiting the WNT/β-Catenin pathway in others. Insufficient levels of hCG are associated with maternal and fetal complications, underscoring the importance of understanding these hormonal dynamics. Notably, preliminary data demonstrate that hCG can substitute for EGF in murine and human enteroid cultures, suggesting an early adaptive mechanism by which the maternal gut anticipates the metabolic demands of pregnancy.
Despite these insights, interactions between pregnancy-related hormones and intestinal adaptations remain poorly understood. Organoids derived from the intestinal stem cell niche offer a promising platform to replicate gut physiology during pregnancy. These models can elucidate mechanisms underlying intestinal adaptation, predict treatment outcomes, and assess the safety of interventions. Furthermore, they hold potential for developing countermeasures against enteropathies, such as celiac disease and inflammatory bowel disease, that negatively impact pregnancy outcomes. Thus, my continuous experiments will explore the integration of organoid technology to enhance our understanding of maternal-fetal health and address unmet needs in pregnancy research.
