Meiosis I Arrest Abnormalities Lead to Severe Oligozoospermia in Meiosis 1 Arresting Protein (M1ap)-Deficient Mice
Meiosis I Arrest Abnormalities Lead to Severe Oligozoospermia in Meiosis 1 Arresting Protein (M1ap)-Deficient Mice
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DOI：
10.1095/biolreprod.111.098673
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Donahoe, Patricia K.
中科院分区：
文献类型：
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作者：
Arango, Nelson Alexander;Li, Li;Donahoe, Patricia K.
减数分裂阻滞蛋白1（Meiosis 1 arresting protein，M1ap）是一个新的脊椎动物基因，在胚胎卵巢和成年睾丸的生殖细胞中特异表达。在雄性小鼠中，M1ap表达，这是目前从精原细胞到次级精母细胞，是进化保守的，并具有特定的空间和时间模式，提示在生殖细胞发育过程中的作用。为了测试其功能，制造了M1ap缺陷的小鼠。而女性卵巢组织学正常，男性表现出睾丸大小减少和无数的管状缺陷，导致严重的少精症和不育。虽然一些生殖细胞在偶线期/粗线期停止，但大多数细胞在停止和进入凋亡之前进入中期I。由于染色体突触异常和未能形成交叉灶，达到中期I的细胞无法在中期板上正确排列其染色体。根据肾小管变性的状态，除精原细胞外，所有生殖细胞均消失;随着进一步恶化，观察到肾小管仅显示支持细胞，这让人联想到人类的支持细胞综合征。我们的研究结果揭示了M1AP作为一种新的生殖细胞基因在男性生殖细胞发育中的重要作用，并表明M1AP的突变可能导致某些男性非梗阻性少精子症。
Meiosis1 arresting protein ( M1ap) is a novel vertebrate gene expressed exclusively in germ cells of the embryonic ovary and the adult testis. In male mice, M1ap expression, which is present from spermatogonia to secondary spermatocytes, is evolutionarily conserved and has a specific spatial and temporal pattern suggestive of a role during germ cell development. To test its function, mice deficient in M1ap were created. Whereas females had histologically normal ovaries, males exhibited reduced testicular size and a myriad of tubular defects, which led to severe oligozoospermia and infertility. Although some germ cells arrested at the zygotene/ pachytene stages, most cells advanced to metaphase I before arresting and entering apoptosis. Cells that reached metaphase I were unable to properly align their chromosomes at the metaphase plate due to abnormal chromosome synapses and failure to form crossover foci. Depending on the state of tubular degeneration, all germ cells, with the exemption of spermatogonia, disappeared; with further deterioration, tubules displaying only Sertoli cells reminiscent of Sertoli cell-only syndrome in humans were observed. Our results uncovered an essential role for M1ap as a novel germ cell gene not previously implicated in male germ cell development and suggest that mutations in M1AP could account for some cases of nonobstructive oligozoospermia in men.