Bernard Laure, Martinat Nadine, Lécureuil Charlotte, Crépieux Pascale, Reiter Eric, Tilloy-Ellul Anne, Chevalier Stéphane, Guillou Florian
Physiologie de la Reproduction et des Comportements, UMR 6175, Institut National de la Recherche Agronomique, Centre National Pour la Recherche Scientifique, Université de Tours, Haras Nationaux, Nouzilly, France.
Reprod Toxicol. 2007 Feb;23(2):158-64. doi: 10.1016/j.reprotox.2006.11.002. Epub 2006 Nov 10.
Any toxicant that affects Sertoli cell development can potentially disturb male fertility. So far, the effects of organochlorine compounds have been poorly investigated in male. Here, we studied the effects of dichlorodiphenyltrichloroethane (DDT), an organochloride pesticide, on Sertoli cells. DDT inhibited the cAMP response to follicle-stimulating hormone (FSH), the major endocrine control of Sertoli cell development, and to a beta2-agonist, isoproterenol. DDT exposure decreased the level of FSH binding sites. Direct adenylyl cyclase activation by Forskolin was unaltered by DDT, while the activation of Galphas by cholera toxin was decreased by DDT. The DDT inhibitory effect on the FSH response was also observed in Ser W3 cells, a Sertoli cell-derived immortalized cell line. All these effects were reproduced by the lipophilic aromatic bisphenol A but not by structurally unrelated CisPlatin. In conclusion, these results are a first step in understanding the molecular basis of DDT deleterious effects in spermatogenesis.
任何影响支持细胞发育的毒物都可能干扰男性生育能力。到目前为止，有机氯化合物对男性的影响研究甚少。在此，我们研究了有机氯农药二氯二苯三氯乙烷（DDT）对支持细胞的影响。DDT抑制了支持细胞发育的主要内分泌调控因子促卵泡激素（FSH）以及β2 - 激动剂异丙肾上腺素所引发的cAMP反应。暴露于DDT会降低FSH结合位点的水平。佛司可林对腺苷酸环化酶的直接激活不受DDT影响，而霍乱毒素对Gαs的激活则被DDT降低。在支持细胞来源的永生化细胞系Ser W3细胞中也观察到了DDT对FSH反应的抑制作用。所有这些效应都可由亲脂性芳香族双酚A重现，但结构不相关的顺铂则不能。总之，这些结果是理解DDT在精子发生中有害作用分子基础的第一步。
