title: Mono-(2-Ethylhexyl) Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta.
abstract: Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2) are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52) signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl)-phthalate (MEHP), increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth.
authors.affiliation: Biomedical Sciences Graduate Program, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, United States of America.|Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Ximi K
authors.initials: XK
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Agarwal
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Parobchak
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Vetrano
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
authors.forename: Todd
authors.initials: T
authors.lastname: Rosen
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002585:Cesarean Section; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007743:Labor, Obstetric / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010795:Phthalic Acids / Q000378:metabolism* / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D021381:Protein Transport; D051841:Transcription Factor RelB / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism; D015854:Up-Regulation; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D003346:Corticotropin-Releasing Hormone; D051546:Cyclooxygenase 2; D016328:NF-kappa B; D010795:Phthalic Acids; D017346:Protein Serine-Threonine Kinases; D051841:Transcription Factor RelB; D000097782:NF-kappaB-Inducing Kinase; C032279:phthalic acid