Impact of Sex and GPER on the Cardiovascular Effects of the Environmental Estrogen Bisphenol A

Abstract

We previously found that the membrane‐bound G‐protein coupled estrogen receptor (GPER) attenuates blood pressure. Environmental estrogens, such as Bisphenol A (BPA) compete for binding at GPER, potentially reducing its beneficial vascular effects. Recent clinical data shows that exposure to BPA is associated with higher blood pressure and cardiovascular disease. The goal of the current study was to assess the effects of BPA on blood pressure in a mouse model and determine the impact of sex and GPER. We hypothesized that BPA administration in female mice would induce a larger increase in blood pressure in comparison to males because of its interference with estrogen's protective vascular effects. Further, we hypothesized that the response to BPA in GPER knockout mice would be diminished. Female (f) and Male (m) wild type (WT) and knockout (KO) mice were administered 5 mg/kg body weight/day of BPA via the drinking water for eight weeks. Blood pressures were measured via tail cuff by volume pressure recording biweekly. Two‐way ANOVA revealed a significant effect of sex (P<0.001) but not GPER deletion (P=0.19) on systolic blood pressure, with females having lower pressures (mWT 148 ± 2.8 vs. fWT 131± 4, P<0.01; mKO 142±3 vs. fKO 128± 3, P<0.05). Diastolic pressures were not statistically different by sex (P=0.08) or GPER deletion (P=0.82). Although the study is ongoing, two weeks after the administration of BPA, there was no significant impact of BPA on blood pressure in any group (P>0.05). In conclusion, since GPER mediates some of the beneficial cardiovascular actions of estrogen, environmental estrogens such as Bisphenol A may act as a “hormonal block” of GPER. Increasing amounts of environmental estrogens may promote cardiovascular problems, especially in aging postmenopausal women.Support or Funding InformationTulane University Newcomb College Lurcy GrantAmerican Heart Association 15GRNT25890021