title: Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein.
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.
authors: Department of Urology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, China.
authors: Lian-Dong
authors: LD
authors: Zhang
authors: Qian
authors: Q
authors: Deng
authors: Zi-Ming
authors: ZM
authors: Wang
authors: Ming
authors: M
authors: Gao
authors: Lei
authors: L
authors: Wang
authors: Tie
authors: T
authors: Chong
authors: He-Cheng
authors: HC
authors: Li
mesh_terms: D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D019833:Genistein / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects*; D007774:Lactation / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D010750:Phosphoproteins / Q000235:genetics; D048789:Phytoestrogens / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013737:Testis / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D052244:Endocrine Disruptors; D010750:Phosphoproteins; D048789:Phytoestrogens; D010968:Plasticizers; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D000098682:Steroidogenic Acute Regulatory Protein; D004051:Diethylhexyl Phthalate; D019833:Genistein; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase; C120361:Cyp11b3 protein, rat; D019405:Cytochrome P-450 CYP11B2