SUN-152 Neonatal Exposure to Estrogen Impairs Intra-ovarian Ovulatory Machinery

Abstract Disclosure: J. Oh: None. C. Park: None. P. Lin: None. S. Zhou: None. C. Ko: None. Endocrine-disrupting chemicals (EDCs) with estrogenic properties are pervasive in the environment, interfering with hormonal signaling pathways and causing long-term reproductive dysfunction. Neonatal exposuse to estrogenic EDCs has been linked to ovarian abnormalties and impaired fertility, yet the underlying mechanisms remain poorly. We recently observed that adult rats neonatally exposed to estradiol for an extended period exhibit a complete lack of corpus lutea (CL), indicating ovulatory failure. This study investigates the hypothesis that prolonged neonatal exposure to an estrogenic EDC disrupts the establishment of the intra-ovarian ovulation machinery. To test the hypothesis, 1-day-old female pups female rats were treated with estradiol benzoate (EB, 0.3mg)-containing microspheres to that were designed to release the EB for 2 weeks. We examined their ovaries on days 7 and 14 by histology. To assess their ovulatory capacity, superovulation was induced at a prepubertal age (23 days) and at an adult age (2 months). The oocytes were collected from oviducts at 16 hours (h) post-hCG injection for oocyte counting, and ovaries were collected at 6 h after hCG injection for gene expression analysis and histology. Histology revealed delayed foliculogenesis the neonatally exposed to estrogen (NeoEE) rats. On day 7, ovaries of NeoEE rats exhibited incomplete germ cell nest breakdown, which was resolved by day 14, indicating delayed follicular development. Superovulation at an adulthood failed to produce oocytes in NeoEE rats, whereas Control rats released an average of 39 oocytes/rat (p<0.001). Ovarian histology showed that NeoEE rats contained numerous cystic follicles but no CL, indicating impaired ovulation rather than foliculogenesis impairment. Further anylsis of immature NeoEE ovaries at 6 h after hCG injection reveald dysregulated expression of genes essential for successful ovulation - endothelin-2 (Edn2), progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2). These results suggest impaired contraction and inflammatory required for ovulation. Taken together, these results show that early-life estrogen exposure causes disruption of ovulatory machinery, providing mechanistic insignt into how EDC exerts long-term adverse effects on female reproductive health. Presentation: Sunday, July 13, 2025