Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol

Prenatal exposure to diethylstilbestrol (DES) is associated with reproductive tract abnormalities, subfertility and neoplasia in experimental animals and humans. Studies using experimental animals suggest that the carcinogenic effects of DES may he transmitted to succeeding generations, To further evaluate this possibility and to determine if there is a sensitive window of exposure, outbred CD-1 mice were treated with DES during three developmental stages: group 1 was treated on days 9-16 of gestation (2.5, 5 or 10 mu g/kg maternal body weight) during major organogenesis; group II was treated once on day 18 of gestation (1000 mu g/kg maternal body weight) just prior to birth; and group III was treated on days 1-5 of neonatal life (0.002 mu g/pup/day). DES-exposed female mice (F-1) were raised to maturity and bred to control males to generate DES-lineage (Fz) descendants. The Fz males obtained from these matings are the subjects of this report; results in Fz females have been reported previously [Newbold ct al, (1998) Carcinogenesis, 19, 1655-1663], Reproductive performance of FZ males when bred to control females was not different from control males. However, in DES Fz males killed at 17-24 months, an increased incidence of proliferative lesions of the rete testis and tumors of the reproductive tract was observed. Since these increases were seen in all DES treatment groups, all exposure periods were considered susceptible to perturbation by DES, These data suggest that, while fertility of the DES Fz mice appeared unaltered, increased susceptibility for tumors is transmitted from the DES 'grandmothers' to subsequent generations.