Biotransformation of Bisphenol A and Its Adverse Effects on the Next Generation

Abstract

Although we are exposed to many chemical substances in routine daily life, the body has metabolic systems capable of detoxifying and eliminating these chemicals. Bisphenol A (BPA) is an endocrine disrupter of great concern because of its estrogenic activity, but stud- ies have indicated no severe adverse effects in adult rodents exposed to BPA due to meta bolic detoxification. BPA is metabolized by glucuronidation mediated by phase II enzymes such as UDP-glucuronosyltransferase. Numerous recent studies in rodents have indicated that maternal BPA exposure causes adverse effects in offspring. It was also shown that bisphenol analogs are efficiently absorbed via the oral route and distributed to the repro ductive tract in pregnant rats, with its residue capable of crossing the placental barrier in the late stage of gestation. Both animal and human studies have demonstrated that BPA and the BPA metabolite BPA-GA are detectable in fetal and amniotic fluid, suggesting the presence of a placental transfer mechanism. In this review, we discuss the pharmacokinet ics of BPA, particularly its (1) metabolism and disposition in the intestine, (2) metabolism and disposition in the liver, and (3) transfer from maternal tissues to the fetus. partially BPA-glucuronide/sulfate diconjugate in males. During pregnancy, bilious excretion of BPA-GA decreases, and reciprocally, venous excretion may increase through MRP. BPA-GA remaining in systemic blood circulation is metabolized by placental or fetal β-glucuronidase, and the resultant BPA would permeate the fetal tissues. MRP, multidrug resistance-associated protein; UGT, UDP-glucuronosyltransferase; ST, sulfotransferase.