Abstract
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 μg/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 E(2) 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.