Deficiency of SPATA46, a Novel Nuclear Membrane Protein, Causes Subfertility in Male Mice
Deficiency of SPATA46, a Novel Nuclear Membrane Protein, Causes Subfertility in Male Mice
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一种新型核膜蛋白 SPATA46 的缺乏导致雄性小鼠生育力低下
DOI：
10.1095/biolreprod.116.140996
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发表时间：
2016-09-01
影响因子：
3.6
通讯作者：
Gui, Yaoting
中科院分区：
文献类型：
--
作者：
Chen, Jianbo;Gu, Yanli;Gui, Yaoting
畸形精子症通常与临床不孕症有关。尽管有许多研究，但男性不育的分子机制仍然知之甚少。在本研究中，我们证明了Spata 46，一个基因编码的一种新的蛋白质的未知功能在小鼠睾丸中发现的缺失，是负责男性不育，不育的原因是精子头部形状异常和精卵融合失败的特点。我们还表明，SPATA 46主要在凝聚的精子细胞中表达，具有高度特异性的定位限制在顶体下区域;由于蛋白质的N-末端的跨膜区，该蛋白质位于核膜上。在亚细胞水平上，SPATA 46缺陷的凝聚精子细胞显示出结构缺陷，包括不连续的核被膜和与异常核形状相关的核中的空腔。此外，在体外，我们确定了SPATA 46的缺乏导致精子在卵的卵黄周间隙周围积累，并且对于与抗SPATA 46抗体孵育的天然精子也观察到相同的现象，这表明SPATA 46对于精卵融合的功能相关性。综上所述，这些结果表明SPATA 46是一种新的蛋白质，参与精子头部的重塑和精卵融合。
Teratozoospermia is generally associated with clinical infertility. Despite numerous studies, the molecular mechanisms underlying male infertility are still poorly understood. In the present study, we demonstrated that deletion of Spata46, a gene encoding a novel protein of unknown function found in mouse testis, was responsible for male subfertility, and the cause of subfertility was characterized as abnormal sperm head shape and a failure of sperm-egg fusion. We also demonstrated that SPATA46 was expressed predominantly in condensed spermatids, with a highly specific localization restricted to the subacrosomal area; the protein is located at the nuclear membrane due to a transmembrane region in the N-terminus of the protein. At the subcellular level, SPATA46-deficient condensed spermatids displayed structural defects consisting of a discontinuous nuclear envelope and a cavity in the nucleus associated with an abnormal nuclear shape. Additionally, in vitro, we determined that the absence of SPATA46 led to accumulation of sperm around the perivitelline space of eggs, and the same phenomenon was also observed for natural sperm incubated with an anti-SPATA46 antibody, suggesting functional relevance of SPATA46 for sperm-egg fusion. Taken together, these results indicated that SPATA46 is a novel protein involved in reshaping of the sperm head and sperm-egg fusion.