Impaired male sexual development in perinatal Sprague-Dawley and Long-Evans hooded rats exposed in utero and lactationally to p,p'-DDE.
Although the pesticide DDT has been banned in the United States for decades, it remains at low levels in the environment. p,p'-DDE, a metabolite of DDT, was recently shown to inhibit the binding of androgens to the androgen receptor and to exert antiandrogenic effects in perinatal Long-Evans (LE) rats at a dose of 100 mg/kg/day administered to pregnant dams. In this study, we compared the effects of p,p'-DDE on male sexual development in offspring of Sprague-Dawley (SD) and LE rats. The chemical was dosed by gavage to pregnant dams at 10 or 100 mg/kg body wt from gestation day 14 to 18. The developing male rats were examined for sexual developmental landmarks, while the effects of p,p'-DDE on androgen receptor expression were evaluated in the testis and other reproductive organs. The tissue dosimetry of p,p'-DDE was also determined at different stages of development following in utero and lactational exposures. The higher p,p'-DDE dose induced a reduction in the male anogenital distance, an increase in retention of male thoracic nipples and alterations in expression of the androgen receptor in either one or both strains. A much weaker response was seen in the lower dose groups. Tissue and body fluid concentrations of p,p'-DDE were similar in the two strains in some tissues but dissimilar in others, particularly in the serum levels. Higher serum p,p'-DDE levels in the LE strain during pregnancy corresponded with an overall greater sensitivity of the LE strain to the antiandrogenic effects of p,p'-DDE. These results support the previous findings of p,p'-DDE antiandrogenicity in LE rats, extend the findings to SD rats, and suggest that the developmental effects of p,p'-DDE on male rat sexual differentiation are minimal at maternal doses below 10 mg/kg/day.
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Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
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Archibeque-Engle
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D000818:Animals; D000833:Animals, Suckling; D001921:Brain / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005485:Flutamide / Q000633:toxicity; D005837:Genitalia, Male / Q000187:drug effects* / Q000254:growth & development; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D007306:Insecticides; D011944:Receptors, Androgen; D013739:Testosterone; D003633:Dichlorodiphenyl Dichloroethylene; D005485:Flutamide