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Bile Acid Metabolism Regulates Ovarian Function: Networks and Reproductive Health Applications
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DOI：10.1017/erm.2026.10035.png)
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Abstract
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BackgroundBile 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.MethodsThis 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.ResultsStudies 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.ConclusionsBA-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.
Keywords:
bile acids
endoplasmic reticulum stress
gut–BAs–ovary axis
ovarian function
polycystic ovary syndrome
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