4 Li BR 46-2.indd

Studies of developmental eff ects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive eff ects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat off spring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg⁄kg body weight (bw)⁄day, GEN 50 mg⁄kg bw⁄day, GEN 400 mg⁄kg bw⁄day, and two combinations of the two compounds (DEHP 250 mg⁄kg bw⁄day + GEN 50 mg⁄kg bw⁄day, DEHP 250 mg⁄kg bw⁄day + GEN 400 mg⁄kg bw⁄day). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coeffi cient, AGD / body weight1 / 3, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bw⁄day), GEN(50mg/kg bw⁄day) or GEN(400mg/kg bw⁄day) alone were not signifi cantly diff erent from the control group. When exposed to (DEHP 250mg/kg bw⁄day +GEN 50mg/kg bw⁄day) together during pregnancy and lactation, serum testosterone concentration, epididymis coeffi cient and Cypal17a1,Scarb1 m RNA expression signifi cantly decreased compared to the control and GEN(50mg/kg bw⁄day). When exposed to (DEHP 250mg/kg bw⁄day +GEN 400mg/kg bw⁄day) together during pregnancy and lactation, AGD / body weight1 / 3, serum testosterone concentration, testis and epididymis coeffi cient and Star, Cypal17a1 mRNA expression appeared signifi cantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most signifi cant alterations in the neonate, especially with GEN at high dose, although the eff ect of the DEHP–GEN mixture on adult off spring should be observed further.