ArticleGastro hep advances2025
Sex Differences in Colonic Inflammation are Driven by Epithelial-Specific Expression of Estrogen Receptor Alpha.
Article in Gastro hep advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Targeting FOXP3 and Regulatory T Cells in Systemic Lupus Erythematosus: Emerging Therapeutic Strategies and Clinical Prospects.Journal of cellular biochemistry · 2026Review
- Pre-Treatment with Estradiol, But not Progesterone, Exacerbates DSS Colitis: Dysregulated Innate Immunity and Impaired Epithelial Damage Response.Inflammation · 2026Article
- Estrogen impacts NOD2-dependent regulation of intestinal homeostasis.PLoS biology · 2026Article
- Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease.International journal of molecular sciences · 2026Review
- Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications.Biology of sex differences · 2026Review
- Effects of combined prenatal exposure to air pollution and maternal stress on immune and dopaminergic gene expression in the gut-brain axis.Brain, behavior, & immunity - health · 2026Article
- Estrogen Receptor Alpha Contributes to Intestinal Inflammation in a Murine Model of Ileitis.Journal of cellular immunology · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Background and Aims: Inflammatory bowel disease patients exhibit altered expression of nuclear estrogen receptors alpha and beta (ERα and ERβ) and G-protein coupled estrogen receptor 1 (GPER1). We previously showed that deletion of ERα protects against intestinal damage selectively in female mice; however, the mechanisms conferring sex-specific protection are poorly understood. The goal of this study was to compare ERα- and ERβ-specific mechanisms contributing to intestinal epithelial function in males and females. Methods: Expression of ERα, ERβ, and GPER1 was evaluated in colonocytes from wild-type male and female mice. Intestinal epithelial cell (IEC)-specific ERα and ERβ knockout mice were developed and challenged with dextran sulfate sodium. Colonic organoids were used to identify estrogen-dependent and estrogen-independent effects on cellular growth, differentiation, and transcriptional regulation in wild-type, ERα-KO, and ERβ-KO IECs. Results: Colonic IECs showed significant expression of ERα, ERβ, and GPER1 as well as Cyp19A1, which catalyzes production of 17β-estradiol (estrogen). Female mice lacking ERα specifically in colonic IECs showed protection from dextran sulfate sodium-induced injury, whereas males showed increased pathology. Organoids derived from male ERα-KO mice showed enhanced proliferation and decreased expression of key functional genes even without exogenous estrogen; however, colonoids derived from female ERα-KO mice showed a protective gene signature. These findings reveal that deletion of ERα contributes to differential effects in male and female IECs, contributing to females' resistance to intestinal injury and inflammation. Conclusion: ERα signaling within IECs drives opposing sex-dependent effects on the development, regenerative capacity, and inflammatory susceptibility of the intestinal epithelium.
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