Bile Acid Metabolism Regulates Ovarian Function: Networks and Reproductive Health Applications.

Abstract

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Bile acids (BAs) are crucial metabolic regulators and signaling molecules involved in lipid metabolism and ovarian function. They primarily affect follicular development, steroidogenesis, and oocyte maturation through systemic circulation and transporter-mediated uptake (e.g., NTCP, ASBT) rather than local ovarian synthesis. Increasing evidence indicates that BA dysregulation is associated with multiple reproductive pathologies. This review is based on the authors' own work and a comprehensive PubMed search of the literature to date on bile acids and female reproduction. PubMed was searched using the terms "bile acid AND ovary," "bile acid AND oocyte," and "bile acid AND reproduction." Retrieved records were screened for relevance to ovarian physiology and pathology, including folliculogenesis, steroidogenesis, granulosa cell function, oocyte maturation, and reproductive disorders, and 51 articles were ultimately included in this review. Studies show significant BA dysregulation in reproductive disorders. In polycystic ovary syndrome (PCOS), elevated glycochenodeoxycholic acid (GCDCA) and taurocholic acid (TCA) correlate with hyperandrogenemia. Excessive BAs can induce endoplasmic reticulum (ER) stress and granulosa cell apoptosis; for example, glycodeoxycholic acid (GDCA) promotes a BAX/BCL-2 imbalance and may accelerate follicular atresia. In contrast, protective BAs such as ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) alleviate ER stress and oxidative damage and may improve oocyte quality. Mechanistically, BAs regulate steroidogenic enzymes (e.g., StAR, CYP11A1) via the nuclear receptor FXR and modulate ovarian function through pathways including EGF-ERK1/2 and PERK-ATF4. Moreover, the gut-BA-ovary axis has emerged as a metabolic hub linking environmental factors to reproductive function, potentially contributing to PCOS pathogenesis and ovarian reserve decline through an integrated regulatory network. BA-mediated signaling networks play important roles in ovarian physiology and reproductive disease. BAs and BA-related pathways may serve as novel biomarkers and therapeutic targets for reproductive disorders.