Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat offspring. 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 le-vel of genes involved in steroidogenesis. Organ coefficient, AGD / body weight(1 / 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 significantly different 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 coefficient and Cypall7a1,Scarbl m RNA expression significantly 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 weightl 3, serum testosterone concentration, testis and epididymis coefficient and Star, Cypall7a1 mRNA expression appeared significantly 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 significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP-GEN mixture on adult offspring should be observed further.