Bisphenol A affects estradiol metabolism by targeting CYP1A1 and CYP19A1 in human placental JEG-3 cells

Abstract

Estradiol, in some way or another, plays a critically important physiologic role in the establishment and maintenance of pregnancy. This study was designed to investigate whether BPA affects the estradiol level of human placental JEG-3 cells, which may contribute to insights into the reproductive toxicity and endocrine disruption of BPA. The JEG-3 cells were treated with increasing concentrations of BPA (0.1 to 50 μM). We observed that BPA significantly reduced estradiol level of JEG-3 cells in a dose-dependent manner, which was accompanied by an increase in CYP1A1 protein level and an inhibition of CYP19A1 protein level. Additionally, by lentiviral transduction, we determined that estradiol level of JEG-3 cells over-expressing CYP1A1 gene was notably decreased and the decrease was of 84.9% compared to the control. Meanwhile, estradiol was almost undetectable in CYP19A1 knockdown group. On the contrary, the group with over-expression of CYP19A1 gene increased estradiol level by 8.6 fold while the CYP1A1 knockdown group increased by 5.6 fold. In summary, our research clearly showed that BPA alters JEG-3 estradiol synthesis and catabolism due to its action on CYP1A1 and CYP19A1 protein levels and may interfere with the normal process of placenta formation and embryonic development during early pregnancy.