SAT-027 Transcriptomic Profiles of the HPG Axis in Males and Females After Prenatal Exposure to the EDC Mixture NeuroMix

Abstract Disclosure: T.M. Milewski: None. M. Streifer: None. L. Thompson: None. D. Sheinhaus: None. A. Hayes: None. A.C. Gore: None. Endocrine-disrupting chemicals (EDCs) are exogenous chemicals ubiquitous in our environment and found in everyday items. Most mammals, including humans, are exposed to changing mixtures of EDCs throughout their lives depending upon environmental factors, including geography, diet, lifestyle, and socioeconomic status. Previous work has revealed that several EDCs alter reproductive physiology and behavior and change gene expression to control reproduction. This study used a rat model to investigate transcriptome changes via 3’ tag-based RNA sequencing (Tagseq) in response to prenatal exposure to a low-dose mixture of environmentally relevant EDCs named NeuroMix (NMX) across the hypothalamic-pituitary-gonadal (HPG) axis. RNA was extracted from the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus (VMN), the anterior pituitary, and the gonads of male and female rats that had been exposed to NMX or control treatments to identify potential gene and pathway targets affected by EDC exposure. Among tissues most affected by treatment were the ARC of males, with 613 differentially expressed genes (DEGs). GO-enrichment analysis revealed genes up-regulated in the ARC of NMX males were involved in synaptic plasticity, while genes down-regulated related to responses to estradiol and glucocorticoids. In females, prenatal NMX exposure showed the largest transcriptome change in the ovaries, with 1295 DEGs. GO-enrichment analysis revealed up-regulation of genes involved in cilium organization and movement, while genes down-regulated in this region were related to immune-related processes. Relatively few DEGs were identified in the testes. Using Qiagen Ingenuity Pathway Analysis, we identified the beta-estradiol pathway to be activated in all NMX female tissues and NMX male pituitary, and inhibited in NMX male, ARC, VMN, and testes. Overall, these results demonstrate that prenatal exposure to NMX affects gene expression across the HPG axis in a sex dependent matter. Presentation: Saturday, July 12, 2025