title: The flame retardant 2,2',4,4'-Tetrabromodiphenyl ether enhances the expression of corticotropin-releasing hormone in the placental cell model JEG-3.
abstract: Polybrominated diphenyl ethers (PBDEs) are chemicals used as flame retardants in household products. After disposing of these items, PBDEs leach from the products by surface water. BDE-47 is a PBDE congener commonly isolated from contaminated food and is the most studied isomer. The placenta is the major source of hormones during pregnancy, and an elevated level of corticotrophin-releasing hormone (CRH) is associated with premature delivery. In the present study, we examined changes in the placental CRH expression under BDE-47 exposure in the JEG-3 cell model system. These placental cells are derived from human choriocarcinoma. Our result showed that this pollutant induced the CRH mRNA expression at 0.5 nM or above in the cells. A similar trend was observed when CRH peptide was determined by Western analysis in the cell lysates. As previous studies have shown the importance of signal transduction pathways in the gene regulation, the status of some protein kinases in the present study was investigated. The phosphorylated PKCα, JNK, and P38 were increased by the toxicant treatment, and administering the specific inhibitors could counteract the induced CRH expression. It appeared that the signaling transduction pathway of PKC was a significant contributor in the transcriptional regulation. Further study by using Electrophoretic Mobility Shift Assay suggested that AP-2 was the ultimate DNA-binding element for the initiation of gene transcription. Because an untimely increased CRH may compromise fetal development and induce preterm birth, the present study suggested that endocrine changes in pregnancy should be taken into consideration in the next assessment.
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Yan Qin
authors.initials: YQ
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences and School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong; Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address: laikleung@cuhk.edu.hk.
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D012333:RNA, Messenger; C511295:2,2',4,4'-tetrabromodiphenyl ether; D003346:Corticotropin-Releasing Hormone; D011494:Protein Kinases
keywords: BDE-47; CRH; Placental cells