Bisphenol-A exposure alters endometrial progesterone receptor expression in the nonhuman primate

Objective: To evaluate the effect of bisphenol-A (BPA), a xenoestrogen endocrine disruptor, on endometrial P receptor (PR) expression in nonhuman primates and human cells. Design: Controlled trial in primates. Setting: University. Animal(s): African green monkeys. Intervention(s): After oophorectomy, BPA (50 mu g/kg/d), E-2, both, or vehicle control were administered. Estradiol and BPA were used in Ishikawa cells. Main Outcome Measure(s): Progesterone receptor expression using immunohistochemistry and quantitative polymerase chain reaction. Result(s): Progesterone receptor expression was increased in E-2-treated primates compared with controls. Exposure to the combination of E-2 and BPA resulted in decreased PR expression compared with E2 exposure alone. In Ishikawa cells treated with E-2, PR expression increased 5.1-fold; however, when Ishikawa cells were simultaneously treated with E-2 and BPA, PR expression was decreased to 0.6-fold that of cells treated with E-2 alone. Conclusion(s): Bisphenol-A alone functions as a weak estrogen. However, when administered with E-2, BPA diminishes E-2-induced PR expression. The estrogen-like effect of BPA reported in exposed humans may be mediated by PR blockade and a resultant decrease in the estrogen inhibition normally imparted by P. Diminished PR expression may underlie previous reports linking BPA exposure to endometrial dysfunction in humans. (Fertil Steril (R) 2011;96:175-9. (C) 2011 by American Society for Reproductive Medicine.)