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

Sung Hoon Kim, Kim SH, SiHyun Cho, Ihm HJ, Hyo Jin Ihm, Young Sang Oh, Oh YS, Heo SH, Seung‐Ho Heo, Seung-Ho Heo, Sail Chun, Chun S, Im H, Hosub Im, Hee Dong Chae, Chae HD, Kim CH, Chung‐Hoon Kim, Chung-Hoon Kim, Byung Moon Kang, Kang BM
The Journal of clinical endocrinology and metabolism · 2015 · vol. 100(12) , pp. E1502–E1511 · doi:10.1210/jc.2015-2478 · PMID:26439087 · W2166874179
article OA: bronze CC0 ⤵ 25 in-corpus citations
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This study found that DEHP exposure increased endometrial cell invasiveness and implant size in mice, with higher phthalate metabolite levels in women with endometriosis, suggesting a role in disease pathogenesis.

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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.

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Condition tags

endometriosis

MeSH descriptors

Diethylhexyl Phthalate Endometriosis Plasticizers Animals Case-Control Studies Cells, Cultured Diethylhexyl Phthalate Endometriosis Endometriosis Female Humans MAP Kinase Signaling System Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Matrix Metalloproteinase 9 Mice, Inbred NOD Mice, SCID p21-Activated Kinases p21-Activated Kinases

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (36)

Cited by (25)

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