Mono-(2-Ethylhexyl) Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta
| Autor: | Aarthi Srinivasan, Anna M. Vetrano, Alex Rosen, Monica Agarwal, Ximi K. Wang, Nataliya Parobchak, Bingbing Wang, Todd Rosen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Small interfering RNA Corticotropin-Releasing Hormone Placenta Phthalic Acids Transcription Factor RelB lcsh:Medicine Protein Serine-Threonine Kinases 010501 environmental sciences Biology 01 natural sciences 03 medical and health sciences Corticotropin-releasing hormone Downregulation and upregulation Pregnancy Internal medicine medicine Humans Gene silencing lcsh:Science 0105 earth and related environmental sciences Cell Nucleus Regulation of gene expression Labor Obstetric Multidisciplinary Cesarean Section RELB lcsh:R NF-kappa B Trophoblasts Up-Regulation Protein Transport 030104 developmental biology Endocrinology Gene Expression Regulation Cyclooxygenase 2 Gene Knockdown Techniques Female lcsh:Q Signal transduction Research Article Protein Binding |
| Zdroj: | PLoS ONE, Vol 11, Iss 1, p e0147013 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0147013 |
| Popis: | 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: | OpenAIRE |
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