Effects of neonatal administration of diethylstilbestrol in male hamsters: disruption of reproductive function in adults after apparently normal pubertal development.

Prenatal and neonatal exposure to natural and synthetic estrogens induces developmental abnormalities in the male and female reproductive systems in several species. In hamsters, a single injection of diethylstilbestrol (DES) on the day of birth induces teratogenic and neoplastic changes throughout the female reproductive tract, apparently via a direct mechanism. The present study investigated the extent and specificity of this phenomenon in the male reproductive system. Male golden hamsters received injections of DES or estradiol-17beta (E2; 100 microg/ animal) on the day of birth and were then killed at 42 (pubertal) and 90 (adults) days of age. Blood was collected for serum testosterone analysis, and the testes and accessory organs were weighed and examined histologically. At the pubertal stage, testicular and accessory organ weights plus serum testosterone levels were similar in untreated animals and in both groups of estrogen-treated animals. Also at the pubertal stage, initiation of spermatogenesis appeared normal in both groups of estrogen-treated animals. In contrast, 100% of the DES-treated animals (n = 22) but none of the E2-treated animals exhibited multiple lesions in the reproductive tract as adults. These DES-induced lesions included cryptorchidism with the testes attached to the abdominal wall, solid testicular tumors, multiple epididymal cysts, and involution of accessory organs. Spermatogenesis was disrupted in the seminiferous tubules, with no developing germ cells, and the interstitial cells were organized as a sheath around the dysfunctional tubules. The epididymis had an involuted epithelial layer with a preponderance of multi-nucleated cells, and seminal vesicle morphology was also abnormal. These DES-specific alterations were not accompanied by any significant change in circulating testosterone levels. We therefore conclude that 1) DES is much more potent that E2 as a neonatal endocrine disrupter in the male hamster, and 2) the DES-specific lesions in the adult male reproductive tract may represent a permanently altered androgen responsiveness in the affected target tissues.