Endocrine Disruptors
Session: Poster Session B
Yiran Zhou, n/a
Postdoc
University of Michigan
Ann Arbor, United States
Yiran Zhou1; Michelle Bellingham2; Richard G. Lea3; Neil P. Evans2; Kevin D. Sinclair3; Vasantha Padmanabhan1
1. Department of Pediatrics, Michigan Medicine, Ann Arbor, Michigan, United States
2. School of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
3. School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, United Kingdom
Abstract Text:
The quantity and quality of oocytes within the ovary are key determinants of female fertility and reproductive success. Oocyte quality is influenced by a combination of morphological, biochemical, genetic, and functional aspects, each of which can be impacted by various internal and external factors, making its evaluation complex. In sheep, as in humans, ovarian reserve—the number of healthy, immature oocytes—is established during fetal development. Exposure to environmental chemicals (ECs) or native steroids can adversely affect ovarian folliculogenesis and oocyte health. Given that humans are simultaneously exposed to multiple ECs, real-life EC exposure models are essential for assessing risk. We previously documented that maternal preconceptional and gestational EC mixture exposure via biosolids, a source of complex mixture of ECs derived from human wastewater treatment, increased the activation and depletion rates of ovarian follicles during prepubertal life (PMID: 39561106). Characterization of GDF9 expression, a key marker of oocyte quality, indicated maternal EC mixture exposure also has a negative impact on the surviving activated follicles in prepubertal animals manifested as decreased likelihood of being an oocyte with higher GDF9 expression in activated follicles (transitory and primary) in prepubertal sheep (ENDO25 poster #8501). Given the complexity of evaluating oocyte quality, this study determined the impact of developmental EC mixture exposure on other key regulators of oocyte survival and development namely expression of c-kit, a receptor for Kit ligand essential for oocyte survival, and accumulation of lipids, which is crucial for oocyte maturation and development. We hypothesized that c-kit expression would be reduced in surviving activated follicles, accompanied by compromised lipid accumulation in oocytes from gonadotropin (Gn)-responsive secondary and antral follicles. 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=11) from preconception to birth. c-kit expression in oocytes from all activated follicles was assessed by immunofluorescence, and lipid accumulation in oocytes from gonadotropin (Gn)-responsive secondary and antral follicles was evaluated using BODIPY staining. Data were analyzed using linear mixed models (lme4 package in R), with treatment as the fixed effect and sire as the random effect, followed by Cohen’s effect size (d) analysis. An increased trend in c-kit expression was observed in primary (P=0.08) and secondary (P=0.05, Cohen’s d=0.9) follicles in BTP prepubertal sheep. Maternal BTP exposure tended to increase lipid accumulation in secondary follicles (P=0.1, Cohen’s d=0.7). These findings indicate that for primary and secondary follicles, oocytes from surviving follicles in BTP-exposed prepubertal sheep tend to exhibit increased developmental potential, as evidenced by c-kit expression. The increased trend in lipid accumulation in secondary follicles may reflect a positive influence as a necessary energy source or a negative effect due to lipotoxicity, an aspect that remains to be investigated.
Funding: NIH R01 ES030374.