Epigenetic Modulation of ESR1 and DNMT3A Following Finasteride Exposure: Implications for Female Reproductive Function

Estrogen receptor 1 (ESR1) plays a central role in female reproductive function by mediating estrogen-dependent regulation of follicular maturation, ovulation, and endometrial preparation for implantation. Dysregulation of ESR1 has been associated with impaired fertility. Similarly, DNA methyltransferase 3A (DNMT3A), a key enzyme in establishing DNA methylation patterns, is essential for oocyte development and proper genomic imprinting. Alterations in DNMT3A activity can compromise oocyte quality and early embryonic development. Finasteride, a 5-alpha reductase inhibitor commonly prescribed for androgenic alopecia and benign prostatic hyperplasia in men, is also used off-label in women for conditions such as hirsutism, acne, and alopecia. Although its endocrine effects are well characterized, its potential epigenetic influence on reproductive signaling pathways remains insufficiently explored. In this study, we investigated the epigenetic impact of finasteride on gonadal signaling pathways using Sertoli cell models. Differential methylation analyses identified multiple genes exhibiting altered epigenetic profiles following finasteride exposure. Notably, ESR1 and DNMT3A were among the dysregulated genes, along with several downstream targets including FAM50B, SNRPN, SMRP1, AP-1, G-protein–related genes, CALML4, PLAG1, SIRT1, SPAG4, and AMPK. These findings suggest that finasteride may influence reproductive-related pathways through epigenetic modulation of ESR1, DNMT3A, and their associated gene networks. While these results do not establish direct causality, they highlight the need for further research to determine whether finasteride may contribute to reproductive dysfunction or infertility in women through epigenetic mechanisms. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.