Genistein attenuates di-(2-ethylhexyl) phthalate-induced testicular injuries via activation of Nrf2/HO-1 following prepubertal exposure

Di-(2-ethylhexyl) phthalate (DEHP) and genistein (GEN) are of the most common endocrine disrupting chemicals (EDCs) present in the environment or the diet. However, investigation of the effects of acute exposure to these two EDCs during prepuberty has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from PND22 to PND35 with vehicle control, GEN 50 mg/kg body weight (bw)/day, DEHP50, 150 and 450 mg/kg bw/day, and combined treatment. Reproductive parameters including testis weight, anogenital distance and organ coefficient were evaluated on PND36. Enzyme activity involved in the regulation of testicular redox state as well as expression of genes and proteins related to anti-oxidative ability and apoptosis were also investigated. The results revealed that by PND36, DEHP treatment had significantly decreased the testis weight, organ coefficient, testicular anti-oxidative enzyme activities and caused tubular vacuolation; however, co-administration of GEN partially alleviated DEHP-induced testicular injuries and enhanced testicular anti-oxidative enzyme activities and upregulated the expression of NF-E2 related factor 2 and heme oxygenase-1, which indicated that GEN partially attenuated DEHP-induced male reproductive system damage through anti-oxidative action following acute prepubertal exposure to DEHP. Thus, GEN may have use in attenuating the damaging effects of other EDCs that lead to reproductive disorders.