Impaired Male Sexual Development in Perinatal Sprague-Dawley and Long-Evans Hooded Rats Exposed in Utero and Lactationally to p , p ′-DDE

Abstract

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.