Nakai A, Suzuki M, Tanabe M
Department of Molecular and Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8397, USA.
EMBO J. 2000 Apr 3;19(7):1545-54. doi: 10.1093/emboj/19.7.1545.
In mammals, testicular temperature is lower than core body temperature, and the vulnerable nature of spermatogenesis to thermal insult has been known for a century. However, the primary target affected by increases in temperature is not yet clear. We report here that male mice expressing an active form of heat shock transcription factor 1 (HSF1) in the testis are infertile due to a block in spermatogenesis. The germ cells entered meiotic prophase and were arrested at pachytene stage, and there was a significant increase in the number of apoptotic germ cells in these mice. In wild-type mice, a single heat exposure caused the activation of HSF1 and similar histological changes such as a stage-specific apoptosis of pachytene spermatocytes. These results suggest that male infertility caused by thermal insult is at least partly due to the activation of HSF1, which induces the primary spermatocytes to undergo apoptosis.
在哺乳动物中,睾丸温度低于核心体温,并且精子发生对热损伤的脆弱性已为人所知达一个世纪之久。然而,温度升高所影响的主要靶点尚不清楚。我们在此报告,在睾丸中表达活性形式热休克转录因子1(HSF1)的雄性小鼠因精子发生受阻而不育。生殖细胞进入减数分裂前期并停滞在粗线期,并且这些小鼠中凋亡生殖细胞的数量显著增加。在野生型小鼠中,单次热暴露导致HSF1激活以及类似的组织学变化,如粗线期精母细胞的阶段特异性凋亡。这些结果表明,热损伤导致的雄性不育至少部分是由于HSF1的激活,其诱导初级精母细胞发生凋亡。