RF22 | PMON03 Sex-specific Effects of Bisphenol-A and its Analogs on Monoamine Levels in the Paraventricular Nucleus

Abstract Bisphenol A (BPA) is known to produce adverse effects on fertility, cardiovascular, and metabolic health. The constraints placed on BPA production led companies to switch to BPA's structural analogs, Bisphenol S (BPS) and Bisphenol F (BPF). These chemicals are used in various equipment, food and drink cans, and paper, permitting widespread exposure. We recently found that prenatal exposure to low levels of these chemicals can increase blood pressure in the offspring. However, the underlying neurobiological mechanism is unclear. We hypothesized that these chemicals could alter the levels of monoamines, specifically in brain regions that regulate cardiovascular function such as the paraventricular nucleus (PVN) of the hypothalamus. Pregnant Sprague Dawley rats were exposed to saline, 5 µg/kg BW of BPA or BPS, or 1 µg/kg BW of BPF from gestation day 6 to 21. Their adult Male and Female offspring were implanted with a radiotelemetry device to measure blood pressure and heart rate levels. Following telemetry, animals were sacrificed, and the brains were collected, frozen and sectioned. The PVN was microdissected, and analyzed for monoamine levels using HPLC-EC. Males exposed to BPA had significant increases in the levels of serotonin (5HT) in the PVN compared to the control group, while a marked increase in 5HT levels were only observed in females exposed to BPF and not BPA (p = 0.0002). No significant changes were observed in Dopamine (DA) or norepinephrine (NE) levels. There were significant sex differences (p<0.0001) and treatment effects (p=0.0003) in the DOPAC/DA turnover ratio with males exposed to BPA, BPS, and BPF having markedly less turnover rates compared to control. No changes in DOPAC/DA turnover was apparent in females. There were significant sex (p<0.0001) and treatment effects (p<0.0001) in the 5HIAA/5HT turnover ratio, with males in the BPA and BPS groups having significantly less turnover compared to controls. In contrast, Females exposed to BPS and BPF had significantly lower 5HIAA/5HT turnover ratios but higher turnover ratios in the groups exposed to BPA. These results indicate that 5-HT production increases markedly in males exposed to BPA and in females exposed to BPF. This is associated with reduced metabolism of 5-HT. This suggests that the significant increases in 5-HT activity in the PVN could possibly contribute to the development of hypertension in these animals. Presentation: Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.