Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells
Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells
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DOI：
10.1073/pnas.0608565103
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发表时间：
2006-12-12
影响因子：
11.1
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Tsai, Meng-Yin;Yeh, Shauh-Der;Chang, Chawnshang
使用Cre-Lox条件敲除策略，我们产生了一个生殖细胞特异性雄激素受体（AR）敲除小鼠（G-AR（-/y））与正常的精子发生。AR（-/y）小鼠附睾中的精子计数和运动力与WT（G-AR（+/y））小鼠相似。此外，生育力测试显示生育力没有差异，并且几乎100%的小于15周的G-AR（-/y）雄性交配的雌性幼崽携带缺失的AR等位基因，这表明在减数分裂期间生殖细胞中发生了有效的AR敲除。总之，这些数据提供了体内证据，表明生殖细胞中没有AR的雄性小鼠仍然可以具有正常的精子发生和生育能力，这表明AR在精子发生过程中的重要作用可能来自以旁分泌方式的间接细胞-细胞通讯。然后，我们比较了G-AR（-/y）小鼠与其他两个睾丸细胞特异性AR（-/y）小鼠和总AR基因敲除雄性小鼠的精子发生和生育力的AR损失的后果。这些结果提供了明确的体内证据，支持细胞中的雄激素/AR信号在精子发生中起着直接的重要作用，而间质细胞中的雄激素/AR信号在调节间质细胞类固醇生成功能中起着自分泌调节作用。在这些小鼠中，完全AR敲除的雄性小鼠具有最严重的缺陷。这些与G-AR（-/y）小鼠的对比数据表明，AR可能在睾丸内的各种细胞中具有不同的作用，以促进小鼠的正常精子发生和雄性生育力。
Using a Cre-Lox conditional knockout strategy, we generated a germ cell-specific androgen receptor (AR) knockout mouse (G-AR(-/y)) with normal spermatogenesis. Sperm count and motility in epididymis from AR(-/y) mice are similar to that of WT (G-AR(+/y)) mice. Furthermore, fertility tests show there was no difference in fertility, and almost 100% of female pups sired by G-AR(-/y) males younger than 15 weeks carried the deleted AR allele, suggesting the efficient AR knockout occurred in germ cells during meiosis. Together, these data provide in vivo evidence showing male mice without AR in germ cells can still have normal spermatogenesis and fertility, suggesting the essential roles of AR during spermatogenesis might come from indirect cell-cell communication in a paracrine fashion. We then compared the consequences of AR loss in the spermatogenesis and fertility of G-AR(-/y) mice with two other testicular cell-specific AR(-/y) mice and total AR knockout male mice. The results provide clear in vivo evidence that androgen/AR signaling in Sertoli cells plays a direct important role in spermatogenesis and in Leydig cells plays an autocrine regulatory role to modulate Leydig cell steroidogenic function. Total AR knockout male mice have the most severe defects among these mice. These contrasting data with G-AR(-/y) mice suggest AR might have different roles in the various cells within testis to contribute to normal spermatogenesis and male fertility in mice.