Graduate School Student Jeju national university, Cheju-do, Republic of Korea
Abstract: Estrogen is an essential endocrine regulator for diverse physiological processes within the female body, including the maintenance of homeostasis. Postmenopausal estrogen deficiency is associated with clinical implications for the osteoporosis, female reproductive tract and gut health. Recent studies have elucidated that estrogen deficiency can impair the gut microbiome, characterized by altered microbial diversity. However, the precise impact by which estrogen deficiency influences gut function, maintaining intestinal stem cells differentiating abilities, and cell composition of the intestine remains unclear. By using intestinal organoids derived from ovariectomized (OVX) mouse intestinal stem cells, we investigated the effects of estrogen deficiency on gut permeability, epithelial regeneration, and stemness. Organoids from OVX mice exhibited increased gut permeability with upregulation of tight junction proteins (ZO-1, Occludin, Claudin-2, Claudin-4) and reduced expression of Lgr5 and CD24, indicating impaired stem cell and Paneth cell function. The administration of 10-9 mM of estradiol (E2) enhanced proliferation (increased budding and Ki67 expression), but it did not fully restore gut barrier integrity. These findings highlight the impact of estrogen deficiency on gut epithelial dynamics and provide better insights into gastrointestinal health in postmenopausal women.
