SAT-244 Effects of endocrine-disrupting chemicals on behavioral and transcriptomic properties during sexual differentiation of the brain in rats

Abstract Disclosure: S.E. Khoury: None. E. Morales-Grahl: None. L. Thompson: None. A.C. Gore: None. N.Y. Eldiraoui: None. This study aims to evaluate how early life exposure of rats to endocrine-disrupting chemicals (EDCs) affects development and sexual differentiation of the brain through molecular and epigenetic programming. Our lab and others have shown that EDC exposure affects the hypothalamus in a sex, time, and exposure dependent manner. These effects lead to changes in gene expression related to gonadal steroid hormone signaling in the brain, shifts in pubertal timing, and altered DNA methylation patterns in hypothalamic regions. Current work is addressing effects of EDC exposure on mating behaviors in rats and whether epigenetic modification in brain regions involved in these behaviors underlie any observed physiological changes. In our lab we use NeuroMix, an EDC mixture containing 9 common industrial chemicals at environmentally relevant doses. We expose rats orally to NeuroMix in early postnatal life through feeding of rat dams, during hormone sensitive periods of brain development in the offspring. Brain tissues are collected at postnatal day 1, adolescence, and during early adulthood and bed nucleus of the stria terminalis and preoptic area of the hypothalamus are dissected for Tag-Seq to look at mRNA expression and whole genome bisulfite sequence (WGBS) to assess changes to gene expression and DNA methylation associated with sex differences at these time points. In adulthood, a subset of early adult males are observed in a natural mating environment and number of and latency to mounts, intromission, and ejaculation are counted. A subset of early adult females are tested and recorded in a paced mating paradigm to uncover differences in female typical sexual behaviors due to NeuroMix treatment. The results of these experiments will provide novel insights into the effects of NeuroMix treatment on sexually dimorphic behaviors and brain epigenetics. Supported by NIH R35 ES035024 Presentation: Saturday, July 12, 2025