Mono-(2-ethylhexyl) phthalate affects the steroidogenesis in rat Leydig cells through provoking ROS perturbation

• Published in: Toxicology in vitro Vol. 26; no. 6; pp. 950 - 955
• Main Authors: Zhao, Yan, Ao, Hong, Chen, Li, Sottas, Chantal M., Ge, Ren-shan, Li, Luxi, Zhang, Yunhui
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2012
• Subjects: Animals; Cells, Cultured; DEHP; Diethylhexyl Phthalate - analogs & derivatives; Diethylhexyl Phthalate - toxicity; Leydig cell; Leydig Cells - cytology; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; MEHP; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Long-Evans; Reactive Oxygen Species - metabolism; ROS; Testosterone - biosynthesis; Oxidative stress; MEHP; DEHP; ROS; Leydig cell
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2012.04.003

► We explored the effect of MEHP on androgen production of rat Leydig cells. ► Low levels of MEHP increased androgen production. ► High levels of MEHP inhibited androgen production. ► In ALCs, MEHP affected androgen production through provoking ROS perturbation.
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 (H2O2). 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.