Reproductive Effects of Early Neonatal Exposure to Diethylstilbestrol or Tamoxifen in Rats

To evaluate the effects of potential estrogenic or anti-estrogenic compounds on reproduction, male and female Sprague-Dawley rats were injected subcutaneously with 50 μg/kg diethylstilbestrol (DES) or 20 mg/kg tamoxifen (TAM) from postnatal day 1 to 5. Growth, estrous cycle, locomotor activity, and reproductive function including masculine sexual behavior, sperm motion, and development of reproductive organs were examined. Decrease in body weight gain and abnormal estrous cycle, such as persistent estrous, or prolonged estrous cycle were observed following early neonatal exposure to DES or TAM, while there was no effect on locomotor activity evaluated in the open field in the DES-or TAM-treated group. A marked decrease in sperm motility was found in the TAM-treated group. Anatomical and histological alterations of reproductive organs were observed in male and female rats in the DES-treated group and in female rats in the TAM-treated group. Early neonatal exposure to DES or TAM affected the masculine sexual behavior, resulting in a marked decrease in the ability to copulate and in fertility. In matings of the DES-or TAM-treated rats and intact rats, none of the treated females copulated successfully, whereas approximately 30% of treated males showed normal fertility. These results suggested that early neonatal exposure to DES or TAM induced more marked reproductive dysfunction after puberty in females than in males.