Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene
Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene
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DOI：
10.1073/pnas.96.14.7986
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Simpson, ER
中科院分区：
文献类型：
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作者：
Robertson, KM;O'Donnell, L;Simpson, ER
精子发生是由促性腺激素和睾酮控制的。然而，最近在雌激素受体cu缺乏的成年小鼠中，雌激素在雄性生殖中的作用被提出。这些小鼠变得不育，主要是因为附睾传出小管对液体重吸收的中断，因此。导致生精上皮破裂[Hess，. R.一、Bunick，D.，李，K. H、Bahr，J.，泰勒，J.A.，Korach，K.美国，和Lubabn，D. B。（1997）Nature（伦敦）390，509-512]，尽管证明了将雄激素转化为雌激素的芳香酶和啮齿动物生精上皮内的雌激素受体，但芳香酶和雌激素在生殖细胞发育中的作用是未知的。我们研究了由于cyp 19基因（ArKO）的靶向破坏而缺乏芳香化酶的小鼠的精子发生。缺乏芳香化酶的雄性小鼠最初是能生育的，但发展为进行性不育，直到它们繁殖幼崽的能力严重受损。芳香化酶缺乏的小鼠在4.5个月和1年之间的精子发生中断，尽管促性腺激素或雄激素没有减少，精子发生主要是在早期精子发生阶段被逮捕，其特征是细胞凋亡和多核细胞的出现增加，圆形和细长的精子细胞显着减少，但支持细胞和早期生殖细胞没有变化。此外，间质细胞增生/肥大明显，推测是循环促黄体激素增加的结果。我们的研究结果表明芳香化酶的局部表达对精子发生是必不可少的，并为雌激素对男性生殖细胞发育和生育力的直接作用提供了证据。
It is well established that spermatogenesis is controlled by gonadotrophins and testosterone. However, a role for estrogens in male reproduction recently was suggested in adult mice deficient in estrogen receptor cu, These mice became infertile primarily because of an interruption of fluid reabsorption by the efferent ductules of the epididymis, thus. leading to a disruption of the seminiferous epithelium [Hess,. R. A., Bunick, D., Lee, K. H., Bahr, J., Taylor, J. A., Korach, K. S., and Lubabn, D. B. (1997) Nature (London) 390, 509-512], Despite the demonstration of the aromatase enzyme, which converts androgens to estrogens, and estrogen receptors within the rodent seminiferous epithelium, the role of aromatase and estrogen in germ cell development is unknown. We have investigated spermatogenesis in mice that lack aromatase because of the targeted disruption of the cyp19 gene (ArKO). Male mice deficient in aromatase were initially fertile but developed progressive infertility, until their ability to sire pups was severely impaired. The mice deficient in aromatase developed disruptions to spermatogenesis between 4.5 months and 1 year, despite no decreases in gonadotrophins or androgens, Spermatogenesis primarily was arrested at early spermatogenic stages, as characterized by an increase in apoptosis and the appearance of multinucleated cells, and there was a significant reduction in round and elongated spermatids, but no changes in Sertoli cells and earlier germ cells. In addition, Leydig cell hyperplasia/hypertrophy was evident, presumably as a consequence of increased circulating luteinizing hormone. Our findings indicate that local expression of aromatase is essential for spermatogenesis and provide evidence for a direct action of estrogen on male germ cell development and thus fertility.