title: 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.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, 361-763 Chungbuk, South Korea.
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Hong
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000818:Animals; D064026:Calbindins; D004054:Diethylstilbestrol / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D064026:Calbindins; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C576506:S100G protein, human; C576508:S100g protein, rat; D004958:Estradiol; D004054:Diethylstilbestrol