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

Biol Res. 2013;46(2):139-46. doi: 10.4067/S0716-97602013000200004.

Abstract

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 (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday), GEN(50mg/kg bwday) or GEN(400mg/kg bwday) alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday) together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday). When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday) together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 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.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP11B2 / genetics
  • Diethylhexyl Phthalate / toxicity*
  • Endocrine Disruptors / toxicity*
  • Female
  • Genistein / toxicity*
  • Genitalia, Male / drug effects*
  • Lactation / drug effects*
  • Male
  • Maternal Exposure / adverse effects
  • Phosphoproteins / genetics
  • Phytoestrogens / toxicity*
  • Plasticizers / toxicity*
  • Pregnancy
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class B / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Testis / drug effects

Substances

  • Endocrine Disruptors
  • Phosphoproteins
  • Phytoestrogens
  • Plasticizers
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B
  • steroidogenic acute regulatory protein
  • Diethylhexyl Phthalate
  • Genistein
  • CYP17A1 protein, rat
  • Steroid 17-alpha-Hydroxylase
  • Cyp11b3 protein, rat
  • Cytochrome P-450 CYP11B2