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Possible Role of Phthalate in the Pathogenesis of Endometriosis: In Vitro, Animal, and Human Data

Authors
 Sung Hoon Kim  ;  SiHyun Cho  ;  Hyo Jin Ihm  ;  Young Sang Oh  ;  Seung-Ho Heo  ;  Sail Chun  ;  Hosub Im  ;  Hee Dong Chae  ;  Chung-Hoon Kim  ;  Byung Moon Kang 
Citation
 JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.100(12) : E1502-E1511, 2015 
Journal Title
 JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 
ISSN
 0021-972X 
Issue Date
2015
MeSH
Animals ; Case-Control Studies ; Cells, Cultured ; Diethylhexyl Phthalate/toxicity* ; Endometriosis/chemically induced* ; Endometriosis/epidemiology ; Female ; Humans ; MAP Kinase Signaling System ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Mice, Inbred NOD ; Mice, SCID ; Phthalic Acids/urine ; Plasticizers/toxicity* ; Prospective Studies ; Stromal Cells/metabolism ; p21-Activated Kinases/genetics ; p21-Activated Kinases/metabolism
Abstract
CONTEXT: Although phthalates were shown to have several negative effects on reproductive function in animals, its role in the pathogenesis of endometriosis remains to be elucidated. OBJECTIVE: We aimed to investigate the in vitro and in vivo effects of di-(2-ethylhexyl)-phthalate (DEHP) and to compare the urinary levels of several phthalate metabolites between women with and without endometriosis. DESIGN: For experimental studies, we used endometrial cell culture and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse models. We also performed a prospective case-control study for human sample analyses. SETTING: The study was conducted at an academic center. MAIN OUTCOME MEASURES: The activities of matrix metalloproteinase (MMP)-2 and 9, cellular invasiveness, phosphorylation of extracellular signal-regulated kinase (Erk), and expression of p21-activated kinase 4 were analyzed in endometrial cells treated with DEHP. The implant size was compared between NOD/SCID mice fed with and without DEHP. Urinary concentrations of several phthalate metabolites were compared between women with and without endometriosis. RESULTS: In vitro treatment of endometrial cells with DEHP led to significant increases of MMP-2 and 9 activities, cellular invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression. The size of the endometrial implant was significantly larger in the NOD/SCID mice fed with DEHP compared with those fed with vehicle. The urinary concentration of mono (2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate, and mono (2-ethyl-5-carboxyphentyl) phthalate were significantly higher in women with endometriosis compared with controls. CONCLUSION: These findings strongly suggest that exposure to phthalate may lead to establishment of endometriosis by enhancing invasive and proliferative activities of endometrial cells.
DOI
10.1210/jc.2015-2478
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Si Hyun(조시현) ORCID logo https://orcid.org/0000-0003-2718-6645
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/156936
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