Evaluation of the bisphenol A-induced vascular toxicity on human umbilical artery

Abstract

Bisphenol A (BPA) is one of the most widely used synthetic compound in the manufacture of polycarbonate plastics and epoxy resins. Worryingly, BPA is an endocrine disrupting chemical (EDC) with an estrogenic, androgenic, or anti-androgenic activities. However, the vascular implications of BPA exposome in pregnancy is unclear. In this sense, the present work proposed to understand how BPA exposure impair the vasculature of the pregnant women. To elucidate this, ex vivo studies were performed using human umbilical arteries to explore the acute and chronic effects of BPA. The mode of action of BPA was also explored by analysing the activity (by ex vivo studies) and expression (in vitro studies) analysis of Ca²⁺ and K⁺-channels and soluble guanyl cyclase. Moreover, in silico docking simulations were performed to unveil the modes of interactions of BPA with the proteins involved in these signalling pathways. Our study showed that the exposure to BPA may modify the vasorelaxant response of HUA, interfering with NO/sGC/cGMP/PKG pathway by modulation of sGC and activation of BKCa channels. Moreover, our findings suggest that BPA can modulate the HUA reactivity, increasing the L-type Ca²⁺ Channels (LTCC) activity, a common vascular response observed in hypertensive disorders of pregnancy.

Keywords: Calcium channels; Endocrine-disrupting chemical; Guanyl cyclase; Molecular docking; Potassium channels; Pregnancy exposome.