title: Mono-(2-ethylhexyl) phthalate affects the steroidogenesis in rat Leydig cells through provoking ROS perturbation.
abstract: Di-2-ethylhexyl phthalate (DEHP), one of the most widely used plasticizers in a number of day-life products, exerts both short-term and long-lasting effects on testicular steroidogenesis during in utero exposure. These actions might be caused by its primary metabolite, mono-(2-ethylhexyl) phthalate (MEHP). In the present study, we investigated the effects of MEHP on steroidogenesis of different stages of rat Leydig cells, progenitor (PLCs), immature (ILCs) and adult (ALCs). Results showed that MEHP affected reactive oxygen species (ROS) generation as well as androgen production in ALCs, but not in PLCs and ILCs, which coincided with hydrogen peroxide (H(2)O(2)). Low concentrations of MEHP (20-200μM) provoked ROS perturbation and caused the stimulation of steroidogenic acute regulatory (StAR), cytochrome P450 side-chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenases (3β-HSD) and 17β-hydroxysteroid dehydrogenases (17β-HSD) activities which elevated T production of ALCs. Contrast to the effect in low doses, high levels of MEHP (2000μM and over) induced overloaded oxidative stress and inhibited steroidogenesis by reducing the activities of these enzymes in ALCs. These results indicated that oxidative stress and subsequent steroidogenic enzymes changes in ALCs were the potential underlying mechanism of the biphasic effects of DEHP on androgen production.
authors.affiliation: School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Ao
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Sottas
authors.forename: Ren-shan
authors.initials: RS
authors.lastname: Ge
authors.forename: Luxi
authors.initials: L
authors.lastname: Li
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: D017382:Reactive Oxygen Species; D013739:Testosterone; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate