title: Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue.
abstract: Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproductive processes. Our lab has previously shown that bisphenol A could regulate corticotrophin releasing hormone and aromatase in cultured placental cells. In the present study, the effect of bisphenol A on these two genes in the placenta was investigated in mice. Pregnant ICR mice were gavaged with bisphenol A at 2, 20 and 200mg/kg body weight/day from E13 to E16 and were euthanized at E17. Compared to the control mice, increased plasma estrogen and corticotrophin releasing hormone were observed in bisphenol A-treated mice. Messenger RNA quantification indicated that placental crh but not cyp19 was induced in mice treated with bisphenol A. Tracking the related signaling pathway, we found that protein kinase C ζ/λ and δ were activated in the placentas of bisphenol A-treated mice. As the gene promoter of crh contains CRE and the half site of ERE, either phospho-PKC or estrogen could stimulate the gene transactivation. These results indicate that bisphenol A might increase plasma concentrations of estradiol, testosterone, corticotrophin releasing hormone and placental phospho-PKC ζ/λ and δ in mice. Ultimately, the incidence of premature birth in these mice could increase.
authors.affiliation: Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Tan
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Tsz Yan
authors.initials: TY
authors.lastname: Wong
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000633:toxicity*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D007527:Isoenzymes; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D060888:Real-Time Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D000098826:Bisphenol A Compounds
chemical_list: D001141:Aromatase; D001559:Benzhydryl Compounds; D003346:Corticotropin-Releasing Hormone; D017362:Cyclic AMP Response Element-Binding Protein; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D007527:Isoenzymes; D010636:Phenols; D011374:Progesterone; D011493:Protein Kinase C; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase; D013739:Testosterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds