MON-169 Developmental Programming: Adverse Effects of Preconceptional and Gestational Exposure to a Real-Life Environmental Chemical Mixture via Biosolids on Oocyte Quality in Prepubertal Sheep

Abstract Disclosure: Y. Zhou: None. M. Bellingham: None. R.G. Lea: None. N.P. Evans: None. K.D. Sinclair: None. V. Padmanabhan: None. Female fertility and reproductive success are determined by ovarian capacity, an index of the number and quality of eggs within the ovary. In sheep, as in humans, the ovarian reserve (i.e., the number of healthy, immature eggs within ovaries) is established during fetal development. Developmental insults, such as inappropriate exposure to native steroids or environmental chemicals (ECs), can adversely affect ovarian folliculogenesis and oocyte health. Given that humans are exposed simultaneously to multiple ECs, which may have additive, synergistic, or antagonistic effects, real-life EC exposure models are essential for assessing risk. We previously documented that maternal preconceptional plus gestational EC exposure via biosolids, a derivative of human wastewater treatment containing a complex mixture of ECs, increased the activation and depletion rate of ovarian follicles in prepubertal sheep (PMID: 39561106). This study tested the hypothesis that the quality of oocytes within surviving activated follicles is also impaired. Ovaries were obtained from EasyCare prepubertal sheep (9.5 weeks), whose mothers were grazed on either biosolids-treated pasture (BTP, n=10) or inorganic fertilizer-treated pasture (Control, n=8) from preconception to birth. Expression patterns of GDF9, a key regulator of oocyte quality and follicular development against VASA background, an oocyte marker, were categorized in activated follicles as absent (no GDF9 expression, VASA evident), low (mild GDF9 expression, VASA evident), and high (strong GDF9 expression, VASA not evident). The ratio of total GDF9 expression to total oocyte area was also quantified in secondary and antral follicles (control 12.7±3.0; BTP 11.6±2.6 follicles/animal). Data were analyzed using ordinal linear regression for categorical data and linear mixed models for relative intensity, incorporating sire effects to account for genetic variance. In the BTP group, the probability of being in a higher quality oocyte category (strong GDF9 expression) was significantly reduced (p<0.01) compared to controls, specifically in the early stages of follicle differentiation (transitory: p <0.001; primary: p<0.05). No differences were found in secondary (gonadotropin-responsive) and antral (gonadotropin-dependent) follicles for either categorical or relative intensity GDF9 data. These findings indicate that prenatal exposure to a real-life EC mixture adversely affects oocyte quality in early-stage (primary and transitory) follicles in prepubertal sheep. Whether this effect persists to adulthood, or whether pubertal hormones overcome this effect, remains to be determined. Funding source: NIH R01 ES030374. Presentation: Monday, July 14, 2025