Sprando R L, Santulli R, Awoniyi C A, Ewing L L, Zirkin B R
Department of Population Dynamics, Johns Hopkins University, Baltimore, Maryland 21205.
J Androl. 1990 Jul-Aug;11(4):344-52.
The authors examined the possibility that ethane 1,2-dimethanesulphonate (EDS) has a cytotoxic effect on spermatogenesis that is not secondary to androgen withdrawal resulting from the well known cytotoxic effect of EDS on Leydig cells. Adult male rats were implanted with polydimethylsiloxane (PDS) capsules containing testosterone (T) and estradiol (E), and were simultaneously injected with EDS. The PDS-TE implants, by inhibiting luteinizing hormone (LH) production, prevented Leydig cells from repopulating the testis and clamped testosterone within the seminiferous tubules at increasing concentrations relative to implant size. In rats that received EDS alone, the number of advanced spermatids per testis was significantly reduced by 2 weeks, but within 8 weeks returned to the numbers maintained in vehicle-injected control rats or in vehicle-injected rats that received testosterone- and estradiol-filled capsules of 24 cm and 0.1 cm, respectively (PDS-24TE). Surprisingly, in rats that received an EDS injection plus PDS-24TE implants, the number of advanced spermatids per testis was significantly reduced at 8 weeks and severe seminiferous tubule atrophy occurred despite the fact that the testosterone concentration was sufficient to quantitatively maintain spermatogenesis in vehicle-injected rats. In rats injected with EDS and implanted with 24 cm testosterone but not estradiol-filled capsules (PDS-24T), the advanced spermatid number per testis was significantly higher than that in the EDS plus PDS-24TE rats, but significantly lower than that in control rats. These results suggest that EDS may have a cytotoxic effect on the seminiferous epithelium that is independent of the elimination of Leydig cells, and the EDS and estradiol act synergistically to exert a profound toxic effect on spermatogenesis.
作者研究了乙烷1,2 -二甲磺酸盐（EDS）对精子发生是否具有细胞毒性作用，这种作用并非继发于EDS对睾丸间质细胞的众所周知的细胞毒性作用所导致的雄激素撤退。成年雄性大鼠植入含有睾酮（T）和雌二醇（E）的聚二甲基硅氧烷（PDS）胶囊，并同时注射EDS。PDS - TE植入物通过抑制促黄体生成素（LH）的产生，阻止睾丸间质细胞重新填充睾丸，并使生精小管内的睾酮浓度相对于植入物大小不断增加。在单独接受EDS的大鼠中，每只睾丸中晚期精子细胞的数量在2周时显著减少，但在8周内恢复到注射赋形剂的对照大鼠或分别接受24 cm和0.1 cm含睾酮和雌二醇胶囊的注射赋形剂大鼠（PDS - 24TE）所维持的数量（PDS - 24TE）。令人惊讶的是，在接受EDS注射加PDS - 24TE植入物的大鼠中，每只睾丸中晚期精子细胞的数量在8周时显著减少，并且尽管睾酮浓度足以在注射赋形剂的大鼠中定量维持精子发生，但仍发生了严重的生精小管萎缩。在注射EDS并植入24 cm含睾酮但不含雌二醇胶囊（PDS - 24T）的大鼠中，每只睾丸的晚期精子细胞数量显著高于EDS加PDS - 24TE大鼠，但显著低于对照大鼠。这些结果表明，EDS可能对生精上皮具有细胞毒性作用，这种作用独立于睾丸间质细胞的消除，并且EDS和雌二醇协同作用对精子发生产生深远的毒性作用。
