FASEB Journal：找到控制雄性产生精子关键基因

2011/11/15 11:05:14

《美国实验生物学会联合会杂志》（FASEB Journal）12月刊上刊登了一篇研究报告称，科学家已经发现**中的雄性激素控制精子生成和男性生育的机理，男性可能采用和女性类似的方式避孕。这 个发现同时也给那些精子数量少和无生育能力的男性带来了希望。虽然上述结果只在小鼠上进行了验证，在其它哺乳动物例如人类身上也可能得到类似结果。

米歇尔·威尔士（Michelle Welsh）博士是论文的合著者，他来自英国爱丁堡的女王医学研究院生殖生育学中心，他说：“这项研究给我们提供了一个新的机会，让我们可以了解雄性激素是如何控制精子产生的，这机理可以为男性不育治疗提供新的思路，同时，为研制出新型男性避孕药提供新的启示。”

威尔士和同事用两组老鼠来进行了研究。第一组老鼠是正常鼠群。第二组老鼠**管周肌样细胞中缺少一个基因，这个基因是用来为男性荷尔蒙受体编码的，相比拥有正常基因组的老鼠来说，缺少基因组老鼠精子产生量将大幅减少，并导致不育。

医学博士杰拉德·韦斯曼（Gerald Weissmann）是《美国实验生物学会联合会杂志》的主编 ，他说：“尽管女性避孕药在60年代以来就已经开始使用，而类似的男性避孕药却一直没有研究出来。这个新研究结果不仅是针对雄性激素和它们的细胞而得到的新型男性避孕药，它同时有望发现新的方法来促进精子生成。” 

Androgen action via testicular peritubular myoid cells is essential for male fertility

Michelle Welsh, Philippa T. K. Saunders, Nina Atanassova, Richard M. Sharpe and Lee B. Smith

The FASEB Journal. 2009;23:4218-4230. doi: 10.1096/fj.09-138347.

Androgens are essential for normal spermatogenesis and male fertility, but how androgens exert this effect remains uncertain. Androgen receptors (ARs) are expressed in several testicular cell types, but continuing uncertainty exists over which cell type mediates androgen control of spermatogenesis. Androgen signaling via Sertoli cells (SCs) is essential for complete spermatogenesis, but the role for androgen signaling via peritubular myoid (PTM) cells is contentious. To address this controversy, we generated PTM-specific AR-knockout (PTM-ARKO) mice in which gross reproductive development was normal, but all PTM-ARKO males were azoospermic and infertile. Testis weight was reduced beyond puberty, and in adulthood there was an 86% reduction in germ cells, compared with wild-type littermates. These changes were not explained by any deficits in testosterone, luteinizing hormone, or follicle-stimulating hormone concentrations. SC function was impaired in PTM-ARKO males, indicated by reduced seminiferous tubule fluid production and reduced expression of some androgen-dependent SC genes. Androgen action via PTM cells is therefore essential for normal testis function, spermatogenesis, and fertility in males. This study also provides the first direct evidence for the importance of androgen-driven stromal-epithelial interactions underpinning the regulation of spermatogenesis; PTM-ARKO mice will enable identification of the new molecular pathways involved.—Welsh, M., Saunders, P. T. K., Atanassova, N., Sharpe, R. M., Smith, L. B. Androgen action via testicular peritubular myoid cells is essential for male fertility.