Maternal-fetal transfer of endocrine disruptors in the induction of Calbindin-D9k mRNA and protein during pregnancy in rat model

Abstract

Estrogenic compounds may influence the growth, differentiation and function in many target tissues, especially in the female reproductive tract during pregnancy. The present study was designed to investigate whether CaBP-9k expression in the maternal tissues and fetal uterus is altered following maternal treatment with diethylstilbestrol (DES), 17beta-estradiol (E2), 4-tert-octylphenol (OP), nonylphenol (NP) and bisphenol A (BPA) during late pregnancy. The expression level of CaBP-9k mRNA in maternal uterus significantly increased when treated with a high dose (600 mg/kg BW per day) of OP and NP. Interestingly, the expression level of CaBP-9k mRNA in extra-embryonic membrane decreased in a dose-dependent manner, suggesting that the expression level of CaBP-9k mRNA in the fetal membrane may be differentially regulated when compared to the expression of CaBP-9k in maternal uterus. In parallel with CaBP-9k mRNA level, a high dose (600 mg/kg) of OP and BPA resulted in an increase of CaBP-9k protein in maternal uterus and low dose of OP and NP increased the expression level of CaBP-9k protein in the placenta. High doses of BPA (400 and 600 mg/kg) resulted in an increase of CaBP-9k protein in maternal uterus and placenta, indicating that these estrogenic compounds may affect both maternal uterus and placenta in the induction of CaBP-9k mRNA and/or protein. In parallel with the expression level of CaBP-9k, mRNA decreased in extra-embryonic membrane, treatment with OP (400 and 600 mg/kg) resulted in a significant decrease of CaBP-9k protein in this tissue, suggesting that both CaBP-9k mRNA and protein may be conversely regulated by OP in extra-embryonic membrane when compared to other tissues. Treatment with OP, NP, and BPA induced a significant increase of CaBP-9k mRNA in fetal uterus, indicating that maternally injected estrogenic compounds may transfer directly from placenta to fetus in the induction of fetal uterus CaBP-9k gene. Taken together, we demonstrated for the first time that maternally injected estrogenic compounds resulted in an increase of CaBP-9k mRNA and/or protein in the maternal tissues (uterus and placenta) and fetal uterus during late pregnancy, suggesting that placenta may not be a reliable barrier against these estrogenic compounds for fetal health.