L. You et al., IMPAIRED MALE SEXUAL DEVELOPMENT IN PERINATAL SPRAGUE-DAWLEY AND LONG-EVANS HOODED RATS EXPOSED IN-UTERO AND LACTATIONALLY TO P,P'-DDE, TOXICOLOGICAL SCIENCES, 45(2), 1998, pp. 162-173
Although the pesticide DDT has been banned in the United States for de
cades, it remains at low levels in the environment. p,p'-DDE, a metabo
lite of DDT, was recently shown to inhibit the binding of androgens to
the androgen receptor and to exert antiandrogenic effects in perinata
l Long-Evans (LE) rats at a dose of 100 mg/kg/day administered to preg
nant darns. In this study, we compared the effects of p,p'-DDE on male
sexual development in offspring of Sprague-Dawley (SD) and LE rats. T
he chemical was dosed by gavage to pregnant dams at 10 or 100 mg/kg bo
dy wt from gestation day 14 to 18. The developing male rats were exami
ned 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 determ
ined at different stages of development following in utero and lactati
onal exposures. The higher p,p'-DDE dose induced a reduction in the ma
le anogenital distance, an increase in retention of male thoracic nipp
les and alterations in expression of the androgen receptor in either o
ne 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, particula
rly 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 rat
s, 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. (C) 1998 society of Toxicology.