Mitochondria-related male infertility
Mitochondria-related male infertility
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DOI：
10.1073/pnas.0604641103
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发表时间：
2006-10-10
影响因子：
11.1
通讯作者：
Hayashi, Jun-Ichi
中科院分区：
文献类型：
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作者：
Nakada, Kazuto;Sato, Akitsugu;Hayashi, Jun-Ichi
大约15%的人类夫妇受到不育的影响，其中大约一半的不育病例可以归因于男性，原因是精子活力低下(弱精子症)或/和数量(少精子症)。由于线粒体基因组(MtDNA)突变是在有生育问题的患者中发现的，因此线粒体呼吸缺陷有可能导致男性不育。为了解决这种可能性，我们使用了一个携带野生型mtDNA和突变mtDNA(Delta MtDNA)的传递线粒体小鼠模型(有丝分裂小鼠)。在这里，我们发现线粒体呼吸缺陷是由Delta mtDNA的积累引起的，导致了有丝分裂小鼠的少精子症和弱精子症。大多数不育的有丝分裂小鼠的精子在中段和细胞核中都有异常。不育的有丝分裂小鼠的睾丸显示减数分裂停滞在合线期，并促进了细胞凋亡。因此，我们在有丝分裂小鼠体内的研究直接表明，哺乳动物精子发生需要正常的线粒体呼吸，而线粒体呼吸缺陷是由于突变mtDNA积累而导致的男性不育。
Approximately 15% of human couples are affected by infertility, and about half of these cases of infertility can be attributed to men, through low sperm motility (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome (mtDNA) mutations are identified in patients with fertility problems, there is a possibility that mitochondrial respiration defects contribute to male infertility. To address this possibility, we used a transmitochondrial mouse model (mito-mice) carrying wild-type mtDNA and mutant mtDNA with a pathogenic 4,696-bp deletion (Delta mtDNA). Here we show that mitochondrial respiration defects caused by the accumulation of Delta mtDNA induced oligospermia and asthenozoospermia in the mito-mice. Most sperm from the infertile mito-mice had abnormalities in the middle piece and nucleus. Testes of the infertile mito-mice showed meiotic arrest at the zygotene stage as well as enhanced apoptosis. Thus, our in vivo study using mito-mice directly demonstrates that normal mitochondrial respiration is required for mammalian spermatogenesis, and its defects resulting from accumulated mutant mtDNAs cause male infertility.