Effects of Gestational and Postnatal Exposure of Diethylstilbesterol on Female Reproduction. Han J., Fielden M.R., Halgren R.G., Zacharewski T.R., Saama P.M., Chou K.

This study examined the effects of maternal exposure to diethylstilbestrol (DES) on the ovulatory function and egg fertilizing ability in the female offspring. Pregnant C57BL/6 mice (F-0), bred with DBA/2 male, were gavaged daily with 0.1cc corn oil containing DES at a nominal dose of 0, 0.1, 1, or 10µg/kg from gestational day 12 to postnatal day 21. No statistically significant effects on gestational index (87.5%, 76.9%, 85.7%, and 64.7%, respectively) or 4 day pup survival (98.1%±1.34, 93.4%±3.0, 95.5%±2.6, and 90.9%±9.1, respectively) were observed. Litter size was significantly decreased in the 10µg/kg treatment group (P < 0.01). Sex ratio (% male) was significantly higher in the 1µg/kg treatment group (P < 0.05) and lower in the 10µg/kg treatment group (P < 0.05). At 3 weeks of age, anogenital distance in the female offspring was longer (4.40±0.11 mm) in the 1µg/kg treatment group that in the control group (4.13±0.07 mm) (P < 0.05). At 3 and 8 weeks of age, eggs from the F-1 females were collected and examined for fertilizing ability in vitro. At 8 weeks of age, the number of eggs ovulated in responding to PMSG and HCG injections was significantly lower in the 10µg/kg treatment group (36.1±17.7/mouse) than that in the controls (41.6±20.3/mouse) (P < 0.05). The numbers of egg ovulated were not different among 3 weeks of age treatment groups. DES did not have any effect on the fertilizing ability of eggs. At 8 weeks of age, the degeneration rate was lower in the 10µg/kg treatment group (4.7±8.2) than in the control group (15.3±14.0) (P<0.02). No relationship between body weight and the number of egg ovulated was observed (P > .1). Results from this study indicated that high dose treatment of DES could compromise female offspring's ovulatory function in adulthood.