HSV type 1 thymidine kinase protein accumulation in round spermatids induces male infertility by spermatogenesis disruption and apoptotic loss of germ cells
HSV type 1 thymidine kinase protein accumulation in round spermatids induces male infertility by spermatogenesis disruption and apoptotic loss of germ cells
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DOI：
10.1016/j.reprotox.2008.11.052
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Kato, Yukio
中科院分区：
文献类型：
--
作者：
Cai, Li-yi;Kato, Takako;Kato, Yukio
据报道，HSV 1型胸苷激酶（HSV 1-TK）引入的转基因啮齿动物和HSV感染的人患有男性不育症。本研究的目的是寻找新的线索，以澄清HSV 1-TK诱导的雄性不育的原因，使用HSV 1-TK转基因大鼠系。两个截短的HSV 1-TK蛋白，37和39 kDa，产生并积累在圆形精子细胞中，其转录起始位点被首次鉴定为全长43 kDa的HSV 1-TK的翻译起始点下游65个碱基。这些年轻的转基因大鼠的精子显示畸形的头部，环状的尾部，头部和尾部的细胞膜缺失。此外，还观察到年龄依赖性生殖细胞损失。TUNEL检测表明，这种生殖细胞的损失是由生殖细胞凋亡增加引起的。这些结果表明，HSV 1-TK在睾丸中的表达不仅导致精子发生异常，而且由于细胞凋亡导致生殖细胞的损失。这些发现为阐明转基因动物和HSV感染患者雄性不育的分子机制提供了新的线索。(C)2008年爱思唯尔公司All rights reserved.
HSV type 1 thymidine kinase (HSV1-TK)-introduced transgenic rodents and HSV-infected humans were reported to suffer male infertility. The present study aimed to find novel clues to clarify the cause of HSV1-TK-induced male infertility using an HSV1-tk transgenic rat line. Two truncated HSV1-TK proteins, 37 and 39 kDa, were produced and accumulated in the round spermatids, and their transcription initiation site was identified for the first time at the 65 base downstream of the translation start point of the full-length 43 kDa HSV1-TK. Spermatozoa from those young transgenic rats showed malformed heads, looped tails, and missing cell membrane in heads and tails. Furthermore, age-dependent germ cell loss was observed. TUNEL assay suggested that this germ cell loss is caused by increased apoptotic germ cell death. These results suggest that the expression of HSV1-TK in testes brings about not only abnormal spermiogenesis but also a loss of germ cells due to apoptosis. These findings could provide a novel clue to elucidate the molecular mechanism underlying male infertility in transgenic animals and HSV-infected patients. (C) 2008 Elsevier Inc. All rights reserved.