Effects of chronic dichlorodiphenyldichloroethylene (DDE) exposure on testosterone production and steroidogenic pathway in male rats.

Endocrine disrupting chemicals (EDCs) are still found in the environment and/or in consumer products. These agents have the capacity to mimic and/or antagonize endogenous hormones and thus perturb the endocrine axis. The male reproductive tract expresses steroid hormone (androgen and estrogen) receptors at high levels and is a major target for EDCs. In the present study, Long-Evans male rats were exposed to dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT) and a chemical present in the environment, in drinking water at 0.1 and 10 μg/L for four weeks. At the end of exposure, we measured steroid hormone secretion and analyzed steroidogenic proteins, including 17β-hydroxysteroid dehydrogenase (17 β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), steroidogenic acute regulatory protein (StAR), aromatase and the LH receptor (LHR). We also analyzed Leydig cell apoptosis ((poly-(ADP-ribose) polymerase (PARP) and caspase-3 in the testes. Testicular testosterone (T) and 17β-estradiol (E2) were both affected by exposure to DDE by displaying altered steroidogenic enzyme expression. DDE exposure also increased expression of enzymes mediating the pathway for programmed cell death, including caspase 3, pro-caspase 3, PARP and cleaved PARP (cPARP). Altogether, the present results demonstrate that DDE directly and/or indirectly can target specific proteins involved in steroid hormone production in the male gonad and suggest that exposure to environmentally relevant DDE levels has implications for male reproductive development and function. Summary: Exposure to environmentally relevant DDE levels has implications for male reproductive development and activity due to its ability to disrupt T and E2 levels when exposed to DDE.