title: Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro.
abstract: Di-(2-ethylhexyl)-phthalate (DEHP) accumulates in the environment, and its exposure is possibly associated with endocrine-related disease in women of reproductive age. The effects of DEHP on human endometrial cells are unknown. We treated human endometrial stromal cells with 10, 100, and 1000 pmol of DEHP and measured reactive oxygen species (ROS) generation, expression levels of antioxidant enzymes, alteration of MAPK/NF-κB signaling and hormonal receptors. DEHP increased reactive oxygen species (ROS) generation and decreased expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), heme oxygenase (HO), and catalase (CAT). By DEHP exposure, p-ERK/p-p38 and NF-κB mediated transcription was increased. Additionally, DEHP induced estrogen receptor-α (ER-α) expression in a dose-dependent manner. This study shows the need for future mechanistic studies of oxidative stress, MAPK/NF-κB signaling, and ER-α as molecular mediators of DEHP-associated endometrial stromal cell alterations, which may be associated with the development of endocrine-related disease such as endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Dong-A University Medical Center, College of Medicine, Dong-A University, Busan, Republic of Korea.
authors.forename: Yeon Jean
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Department of Obstetrics and Gynecology, Dong-A University Medical Center, College of Medicine, Dong-A University, Busan, Republic of Korea.
authors.forename: Seung Bin
authors.initials: SB
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, Dong-A University Medical Center, College of Medicine, Dong-A University, Busan, Republic of Korea. Electronic address: hmsobgy@dau.ac.kr.
authors.forename: Myoungseok
authors.initials: M
authors.lastname: Han
mesh_terms: D000328:Adult; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017697:Premenopause; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D004051:Diethylhexyl Phthalate; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Di-(2-ethylhexyl)-phthalate; Endometrial stromal cells; Estrogen receptor-α; Oxidative stress