Shetty Gunapala, Weng Connie C Y, Porter Karen L, Zhang Zhen, Pakarinen Pirjo, Kumar T Rajendra, Meistrich Marvin L
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
Endocrinology. 2006 Jul;147(7):3563-70. doi: 10.1210/en.2006-0159. Epub 2006 Apr 20.
The jsd mice experience a single wave of spermatogenesis, followed by an arrest of spermatogenesis because of a block in spermatogonial differentiation. Previous pharmacological and surgical studies have indicated that testosterone (T) and low scrotal temperatures but not FSH block spermatogonial differentiation in jsd mice. We sought to test these observations by genetic approaches by producing male jsd mutant mice with either defective androgen receptor (AR, Tfm mutation) or a deficiency of FSH (fshb(-/-)). In adult jsd-Tfm double-mutant mice, the tubule differentiation index was 95% compared with 14% in jsd littermates, suggesting that general ablation of AR function restored spermatogonial differentiation in jsd mice. The results indicated that this enhancement of differentiation was primarily a result of elevation of temperature caused by the cryptorchid position of the testis in jsd-Tfm double-mutant mice, which resulted from the lack of AR in the gubernaculum. The low levels of T were not a factor in the release of the spermatogonial differentiation block in the jsd-Tfm mice, but we were unable to determine whether inactivation of AR in the adult jsd testis had a direct effect on the restoration of spermatogonial differentiation because the elevated temperature bypassed the T-induced block in spermatogonial differentiation. Although spermatogonia were indeed present in adult jsd-fshb double-mutant mice and were capable of differentiation after androgen deprivation, these mice had a tubule differentiation index of 0%, ruling out the possibility that endogenous FSH inhibited spermatogonial differentiation in jsd mice. The results are consistent in support of the hypothesis that inhibition of spermatogonial differentiation in jsd mice is a result of T acting through the AR only at scrotal temperatures.
jsd小鼠经历一波精子发生过程，随后由于精原细胞分化受阻而导致精子发生停滞。先前的药理学和手术研究表明，睾酮（T）和阴囊低温而非促卵泡生成素（FSH）可阻断jsd小鼠的精原细胞分化。我们试图通过基因方法验证这些观察结果，即培育出雄激素受体缺陷（AR，Tfm突变）或FSH缺乏（fshb(-/-)）的雄性jsd突变小鼠。在成年jsd-Tfm双突变小鼠中，曲细精管分化指数为95%，而jsd同窝小鼠为14%，这表明AR功能的全面缺失恢复了jsd小鼠的精原细胞分化。结果表明，这种分化增强主要是由于jsd-Tfm双突变小鼠睾丸隐睾位置导致的温度升高，这是由于睾丸引带中缺乏AR所致。低水平的T不是jsd-Tfm小鼠精原细胞分化阻滞解除的因素，但我们无法确定成年jsd睾丸中AR的失活是否对精原细胞分化的恢复有直接影响，因为温度升高绕过了T诱导的精原细胞分化阻滞。虽然成年jsd-fshb双突变小鼠中确实存在精原细胞，并且在雄激素剥夺后能够分化，但这些小鼠的曲细精管分化指数为0%，排除了内源性FSH抑制jsd小鼠精原细胞分化的可能性。这些结果一致支持以下假说：jsd小鼠精原细胞分化的抑制是T仅在阴囊温度下通过AR起作用的结果。
