Mono-(2-Ethylhexyl) Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta.

Autor:	Wang XK; 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., Agarwal M; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America., Parobchak N; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America., Rosen A; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America., Vetrano AM; Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America., Srinivasan A; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America., Wang B; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America., Rosen T; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2016 Jan 11; Vol. 11 (1), pp. e0147013. Date of Electronic Publication: 2016 Jan 11 (Print Publication: 2016).
DOI:	10.1371/journal.pone.0147013
Abstrakt:	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.
Databáze:	MEDLINE
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