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Your Environment. Your Health.

Role of PXR Protein in Early-life BPA Exposure and Atherosclerosis

Changcheng Zhou, Ph.D.
University of Kentucky
R01ES023470, R21ES022745

NIEHS grantees provided mechanistic evidence linking maternal bisphenol A (BPA) exposure to an increased risk of atherosclerosis, which is the narrowing of arteries due to plaque buildup, in offspring. The findings in mice showed how BPA could activate the pregnane X receptor (PXR), a protein in humans that detects foreign substances in the body and regulates several genes involved in metabolizing them.

Previous studies have shown that PXR activation can accelerate atherosclerosis development in mice. Although BPA has been shown to activate PXR in human cells, it does not activate PXR in mice or rats. To investigate the effects of BPA on atherosclerosis in mice, the researchers developed an atherosclerosis-prone mouse model with human-like PXR. They compared the effects of BPA exposure in atherosclerosis-prone mice with and without the humanized PXR.

The researchers reported that exposure to BPA around birth increased atherosclerosis in atherosclerosis-prone adult male, but not female, PXR-humanized mice. In these mice, they also observed increased expression of the fatty acid transporter CD36, which is a direct PXR target gene that plays a role in atherosclerosis development.

According to the authors, the study is the first to report the effect of maternal BPA exposure on atherosclerosis development in male offspring. Because PXR can be activated by endocrine-disrupting chemicals other than BPA, the authors added that activation of human PXR should be considered when assessing the risk of endocrine-disrupting chemicals.

Citation: Sui Y, Park SH, Wang F, Zhou C. 2018. Perinatal bisphenol A exposure increases atherosclerosis in adult male PXR-humanized mice. Endocrinology 159(4):1595–1608.

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