7871 Investigating The Impact Of Prenatal Exposure To A Mix Of Endocrine-Disrupting Chemicals On Development: Behavioral, Physiological, And Transcriptomic Analyses

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Abstract Disclosure: M.R. Streifer: None. L. Thompson: None. A.C. Gore: None. In recent decades, there has been a growing concern surrounding the presence of endocrine-disrupting chemicals (EDCs) in our environment and their potential implications on human health. Among these, prenatal exposure and subsequent effects on the developing neuroendocrine system have emerged as a subject of interest. This study aims to define the long term developmental, behavioral, and molecular effects of prenatal exposure to NeuroMix, a complex mixture of environmentally relevant EDCs. To this end, pregnant rat dams were fed either NeuroMix or vehicle, exposing the developing fetuses during critical periods of neuroendocrine development. The exposed offspring (F1 generation) were the experimental subjects, which were allowed to mature to adulthood, underwent behavioral testing, then were euthanized for brain tissue collection. Our study revealed noteworthy sex-specific effects, whereby exposed males exhibited reduced bodyweight and anogenital index, as well as delayed puberty. In contrast, females displayed no overt developmental abnormalities but exhibited heightened risk-taking behaviors in controlled behavioral experiments like the light:dark box. To unravel the molecular underpinnings of these observed effects, 3’ Tag-sequencing and transcriptomic analyses were performed on the arcuate nucleus (ARC) and ventromedial nucleus (VMN), two hypothalamic nuclei involved in hormonal regulation, metabolism, fear-based behaviors, and development. Results of Ingenuity Pathway Analysis (IPA) unveiled differentially expressed genes in both males and females, highlighting key pathways implicated in mitochondrial dysfunction and estrogen receptor signaling. Other notable pathways identified were related to cancer, neurological disorders, and endocrine system disorders. This comprehensive investigation highlights the impact of prenatal exposure to EDCs, influencing not only physiological parameters like body weight and puberty onset, but also behavioral phenotypes indicative of neurobiological alterations. The identification of disrupted molecular pathways provides valuable insights into the potential mechanisms linking EDC exposure to adverse health outcomes, warranting further exploration and consideration in the context of human health and environmental policy. Grant support: R01 ES029464. Presentation: 6/1/2024