Postnatal Impact of Bisphenol S Exposure on Oxidative Stress-Mediated Endothelial Dysfunction
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2022-03-24
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Abstract
Bisphenols are synthetic polymers used in the production of household plastics; exposure to this compound has been associated with a multitude of adverse health outcomes. Bisphenol A (BPA) is the most well known and widely studied bisphenol. After several countries introduced regulatory bans on the sale and import of baby products containing BPA, manufacturers replaced BPA with structural analogues such as BPS and BPF. Although links between BPA exposure and reproductive, developmental, and metabolic diseases have been widely reported, few studies have investigated the impact of BPA on the vasculature and very little is known regarding the structural analogues that are increasingly replacing BPA. Bisphenols have been shown to increase the production of reactive oxygen species (ROS) in different cell types. Excess ROS in endothelial cells interacts with nitric oxide (NO), reducing is bioavailability. Therefore, BPS-induced ROS production in endothelial cells may impair NO-mediated vasodilation. Aim 1 of this study sought to determine whether BPS exposure decreases NO availability through the increased production of ROS. Findings demonstrated increased ROS production, decreased NO availability and uncoupling of endothelium NO synthase (eNOS) in human umbilical vein endothelial cells (HUVEC)exposed to BPS. RT-qPCR analysis determined that BPS reduced expression of antioxidant genes, while activity of the antioxidant was inhibited with BPS exposure. Aim 2 of this study determined whether postnatal exposure to BPS in C57BL/J6 mice impaired endothelium-dependent vasodilation in resistance vessels. Male and female mice were exposed to an environmentally relevant dose of BPS from the age of weaning (3 weeks) to early adulthood (12 weeks). Pressure myography evaluation of isolated mesenteric arteries demonstrated a reduced maximal response (Emax) to the NO-dependent dilator, methacholine, BPS-exposed male mice. Postnatal exposure in vivo had no measured effect on bodyweight, body composition, insulin sensitivity, or serum lipid peroxidation. In conclusion, BPS exposure reduced NO availability, leading to impaired endothelium-dependent dilation in the microvessels due toROS-mediated eNOS uncoupling. Therefore, exposure to BPS may contribute to the onset of vascular disease
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Easson, S. (2022). Postnatal Impact of Bisphenol S Exposure on Oxidative Stress-Mediated Endothelial Dysfunction (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.