title: Protective effect of (±)α-tocopherol on brominated diphenyl ether-47-stimulated prostaglandin pathways in human extravillous trophoblasts in vitro.
abstract: Brominated diphenyl ether (BDE)-47 is a prevalent flame retardant chemical found in human tissues and is linked to adverse pregnancy outcomes in humans. Because dysregulation of the prostaglandin pathway is implicated in adverse pregnancy outcomes, the present study investigates BDE-47 induction of prostaglandin synthesis in a human extravillous trophoblast cell line, HTR-8/SVneo, examining the hypothesis that BDE-47 increases generation of reactive oxygen species (ROS) to stimulate the prostaglandin response. Treatment with 20 μM BDE-47 significantly increased mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2) at 4, 12 and 24 h, and 24-h treatment significantly increased cyclooxygenase (COX)-2 cellular protein expression and prostaglandin E2 (PGE2) concentration in culture medium. The BDE-47-stimulated PGE2 release was inhibited by the COX inhibitors indomethacin and NS398, implicating COX activity. Exposure to 20 μM BDE-47 significantly increased ROS generation as measured by carboxydichlorofluorescein fluorescence, and this response was blocked by cotreatment with the peroxyl radical scavenger (±)-α-tocopherol. (±)-α-Tocopherol cotreatment suppressed BDE-47-stimulated increases of PGE2 release without significant effects on COX-2 mRNA and protein expression, implicating a role for ROS in post-translational regulation of COX activity. Because prostaglandins regulate trophoblast functions necessary for placentation and pregnancy, further investigation is warranted of BDE-47 impacts on trophoblast responses.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address: heaven@umich.edu.
authors.forename: Hae-Ryung
authors.initials: HR
authors.lastname: Park
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Loch-Caruso
mesh_terms: D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D000071876:Prostaglandin-E Synthases; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D020011:Protective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C511295:2,2',4,4'-tetrabromodiphenyl ether; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D024502:alpha-Tocopherol; D015232:Dinoprostone
keywords: Cyclooxygenase (COX)-2; HTR-8/SVneo cells; Human placental cells; Polybrominated diphenyl ethers (PBDEs); Prostaglandins; α-tocopherol