Molecular mechanisms of the influences of endocrine disruptors on spermatogenesis using Japanese eel.

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In order to understand the estrogenic influence of endocrine disruptors on spermatogenesis, I analyzed the function of endogenous estrogen : estradiol-17β (E2) on spermatogenesis. E2 was present in the serum and its receptor was expressed in the testis during the whole process of spermatogenesis. Spermatogonial stem cell renewal was induced by E2 implantation but was suppressed by tamoxifen (antagonist of estrogen). In vitro, E2 also stimulates spermatogonial stem cell division in cultured testicular tissue, confirming the in vivo observations. These resuits clearly show that estrogen is an indispensable "male hormone" in early spermatogenetic cycle.To determine the genes regulated spermatogonial stem cell renewal directly, we have applied an expression screening to identify genes whose expression is regulated by (E2) in testes. We found one previously unidentified cDNA clone that was up-regulated by E2 stimulation, and named it eSRS34 cDNA. The function of eSRS34 was examined using in … More vitro systems. Recombinant eSRS34 produced by vaculovirus system induced spermatogonial mitosis in testicular organculture. We conclude that eSRS34 is "spermatogonial stem cell renewal factor".Among the estrogenic endocrine disruptors, the influences of diethylstilbestrol (DES), para-nonylphenol (NP) and bis-phenol A on spermatogenesis was examined in vitro testicular organ culture system. The treatments with these chemicals alone stimulates spermatogonial stem cell renewal in the same manner of E2 treatment. In addition, under the existence of 11-ketotestosterone (11-KT), the major androgen in teleosts, these three chemicals did not disturb the progress of spermatogenesis, but the treatment of DES or NP stimulated the remarkable enlargement of Sertoli cell, its structure was similar that of the phagocytotic cells. As a result of the morphological changes of Sertoli cells, the number of germ cells was decreased. These results indicate that DES and NP affected the spermatogenesis by the existenee of the androgen. Less