Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2

Preeclampsia leads to adverse outcomes for pregnant women. Bisphenol A (BPA) is an environmental endocrine disruptor and has been shown to be positively associated with increased risk of preeclampsia in human studies. We investigated whether BPA exposure causes preeclampsia-like features in pregnant mice and the associated underlying mechanisms. Experiments were performed in animal models and cell cultures. In pregnant mice, BPA-exposed mice exhibited preeclampsia-like features including hypertension, disruption of the circulation, and the placental angiogenesis biomarkers fms-related tyrosine kinase 1 and placenta growth factor, and glomerular atrophy; urinary protein was not affected. These preeclampsia-like features correlated with increased retention of smooth muscle cells and reduced vessel areas at the junctional zone of the placenta. In addition, there were disrupted expression of invasion-related genes including increased tissue inhibitors of metalloproteinases, decreased metalloproteinases, and W...