ODP269 Impacts of Gestational Bisphenol A Exposure on Adult Hypothalamic Neurogenesis

Abstract

Abstract Regulation of physiological homeostasis by the hypothalamus is influenced by low basal levels of adult neurogenesis arising from proliferative cell populations in various hypothalamic regions. Adult hypothalamic neurogenesis is involved in maintenance of energy homeostasis and is responsive to energy balance disruptions. Hormones such as oestradiol interact with energy balance disruptions to alter rates of prenatal and adult neurogenesis, demonstrating sensitivity of hypothalamic neural progenitor cells to endogenous hormones. We previously showed that gestational exposure to the hormone mimic bisphenol A (BPA) accelerates embryonic hypothalamic neurogenesis with lasting effects on hypothalamic function into adulthood (1). The impact of gestational exposure to BPA on hypothalamic progenitors that contribute to adult neurogenesis has not been explored. The present study examines the interaction between energy balance disruptions via high-fat diet and the lasting impact of gestational BPA exposure on adult hypothalamic neurogenesis. Pregnant dams were either fed a control diet or chow laced with a low dose of BPA (50 μg per kg diet), then offspring were placed on low-fat or high-fat diet throughout adolescence (postnatal day (P) 5-35) and weighed every 5 days to assess physical changes. Intraperitoneal injections of BrdU were conducted twice a day from P45-53 to mark proliferating cells. To identify changes in the number and/or type of proliferating cells as a result of gestational BPA exposure and diet changes, brains from mice sacrificed at P54 and P75 were co-stained for BrdU and cell type specific markers to label neurons, oligodendrocytes, or astrocytes. Results showed that in adolescent animals on low-fat diet, BPA exposure decreased weight gain compared to controls (7.68±4.22 g vs. 8.50±3.98g;p< . 0001; n≥20 per group). Similarly, in adolescent animals on high-fat diet, BPA exposure decreased weight gain compared to controls (8.54±2. 02 g vs. 9.97±4.89g;p< . 0001; n≥20 per group). There was no impact on weight gain in adult male mice, however in adult female mice on low-fat diet, BPA exposure decreased weight gain compared to controls (18.33±1.45 g vs. 18.97±1.50 g;p=. 019; n≥7 per group). The opposite effect was seen in adult female mice on high-fat diet, where BPA exposure increased weight gain compared to controls (20. 07±1.51 g vs. 19.62±1.478 g;p=. 050; n≥7 per group). Preliminary data demonstrate a trending increase in hypothalamic neurogenesis in adult P54 females on low-fat diet exposed to BPA compared to controls (200.15±34.85 BrdU+/NeuN+ cells vs. 69. 00±6. 00 BrdU+/NeuN+ cells, n=2) and on high-fat diet exposed to BPA compared to controls (169.65±101.65 BrdU+/NeuN+ cells vs. 50.15±17.85 BrdU+/NeuN+ cells, n=2). These data suggest BPA may have an estrogenic effect on hypothalamic neural progenitors, resulting in disruptions to adult hypothalamic neurogenesis and energy balance homeostasis. Reference: (1) Nesan et al., Science Adv. 2021 May 28;7(22): eabd1159 . Presentation: No date and time listed