| It is well-known that estrogenic environmental endocrine disruptors affect the structure and function of male reproduction system. It have been reported that estrogenic environmental endocrine disruptors have negative effects on reproduction system of fetal and neonatal male animals. But so far it is still unclear that the effects of these disruptors on adult animals. Diethylstilbestrol (DES), as an ideal medicine to study the function of environmental estrogenic hormone, is a kind of lipidic hormone with a long half-life, which easily accumulated itself in adipose tissues. The objective of the present study was to build a proper animal model and to investigate the effect of DES on spermatogenesis and sperms maturation of male animals. These data will help for elucidating the mechanism of environmental estrogenic disruptors inducing abnormal spermatogenesis in adult animals. Therefore, adult rat, mice and hamster were treated by subcutaneous injection of various doses DES (0.01, 0.1 and 1.0 mg/kg body weight). After DES treated, the changes on the morphology of testes and epididymis, the number of apoptotic cells, the levels of NO and polyamine (putrescine, spermine and spermidine), and the expressions of proto-oncogenes (Bcl-2 and p53), cadherin adherens molecules, nitric oxide synthase (eNOS and iNOS) were measure in adult hamster by light microscopic and transmission electron microscopy, TUNEL staining (TdT-mediated dUTP nick end labeling), histochemical staining, thin-layer chromatography, and immunolohisto-chemical staining, respectively. The results were demonstrated as follows:1. The subcutaneous injection of 1.0 mg/kg DES could induce obviously abnormal spermatogenesis in the adult male hamster. All changes after DES treatment were more prominent in the adult hamster than in the adult rat and mice.2. After DES treatment, the testes atrophy was obvious, and lots of apoptotic cells were found in spermatogenic cells in adult male hamster, especially in spertocytes and spermids. The reduction of leydig cells and malformed sertoli cells were observed in the DES-treated hamsters. All these changes were dose-dependent. In the 1.0 mg/kg dose group, the number of apoptotic spermatogenic cells increased by 44 folds with a loss of 57% in testes weight.3. DES could result in epididymis atrophy with the apoptosis of epididymis epithelial cells. Both the number of glucose-proteins in epididymis and that of mast cells in cauda epididymis increased significantly.4. After DES treatment, the expression of Bcl-2 and p53 in spermatogenic cells significantly increased, and increased to 96.9% (Bcl-2, 1.0mg/kg DES) and 88.9% (p53, 1.0mg/kg DES), especially in spermatocytes and round spermatids. However, the expression of cadherin obviously decreased. DES could increase the expression of Bcl-2 and p53, and decrease the expression of cadherin by a dose-dependent way.5. After DES treated, in hamster testes the expression of iNOS and eNOS in spermatogenic cells significantly increased, while the levels of NO increased obviously by a dose-depentment way.6. DES could induce testes produce high levels of polyamines (putrescine, spermine and spermidine), especially spermine by a dose-depentment way.In conclusion, one the hand, DES could increase the expression of the proto-oncogenes (Bcl-2, p53) and nitric oxide synthase (eNOS and iNOS) in spermatogenic cells, and increase the levels of NO and polyamine in testes, but decrease the expression of cadherin adherens molecules. These changes in testes could induce a lot of spermatogenic cells apoptosis, and decrease the number of leydig cells, thus result in abnormal development of adult animal spermatogenic cells. On the other hand, DES could induce epididymis epithelial cells apoptosis, increase the levels of glucose-proteins in epididymis. Theses changes would influent on sperm maturation, result in adult animal abnormal spermatogenesis.
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