Protective effects of vitamin E against reproductive toxicity induced by di(2-ethylhexyl) phthalate via PPAR-dependent mechanisms

Objective: To investigate the protective/ameliorative effects of vitamin E on di-2-(ethylhexyl) phthalate (DEHP)-induced reproductive toxicity, particularly in testicular toxicity in male rats, emphasizing peroxisome proliferator-activated receptor (PPAR)-dependent mechanism.

Methods: Sprague-Dawley females were exposed by oral route to DEHP alone or associated with vitamin E from gestation day (GD) 12.5 to postnatal day (PND) 3 according to the following treatment regimens: vehicle control (corn oil), vitamin E (200?mg/kg)+corn oil, DEHP (500?mg/kg)+corn oil, and DEHP (500?mg/kg)+vitamin E (200?mg/kg)+corn oil. Variables including litter size, sex ratio, pup weight, post-implantation losses, and the number of viable pups were also assessed. Three male pups per litter were randomly selected and necropsied to measure paired testes weight, apoptosis, and gene expression on PND 3. To evaluate the long-term protective effects of vitamin E, three randomly selected males were necropsied to measure testis histology on PND 70.

Results: Supplementation of vitamin E (200?mg/kg) reduced malformations, increased testes weight and prevented the maternal bodyweight loss induced by DEHP. Litter size, sex ratio, and number of viable pups were unaffected, but vitamin E co-administration declined testicular cell apoptosis, decreased the PPARs expression, and protected testis histology.

Conclusions: Vitamin E cotreatment showed protective effects against DEHP-induced testicular toxicity, including reproductive malformations, testicular weight, apoptosis and histology, and the mechanisms maybe associated with PPARs.