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

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. •BPA significantly reduced the estradiol level of JEG-3 cells in a dose-dependent manner.•BPA exerted an increase in CYP1A1 protein expression and an inhibition of CYP19A1 protein expression in JEG-3 cells.•Both CYP1A1 and CYP19A1 are involved in BPA induced decrease of estradiol in JEG-3 cells.