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Ccdc87 对于精子功能和男性生育能力至关重要。

Ccdc87 is critical for sperm function and male fertility.

机构信息

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Shanghai Foreign Language School, Shanghai, China.

出版信息

Biol Reprod. 2018 Oct 1;99(4):817-827. doi: 10.1093/biolre/ioy106.

Abstract

Male infertility has become an increasingly common health concern in recent years. Apart from environmental factors, nutrition, lifestyle, and sexually transmitted diseases, genetic defects are important causes of male infertility. Many genes have been demonstrated to be associated with male infertility. However, the roles of some functional genes in infertility, especially those that are specifically expressed in the reproductive system, remain to be elucidated. Here, we demonstrated that the testis-specific gene coiled-coil domain-containing 87 (Ccdc87) is critical for male fertility. Reverse-transcriptase polymerase chain reaction and western blot analyses revealed that the Ccdc87 mRNA and protein were only expressed in mouse testis. Ccdc87 expression first appeared at postnatal day 14 and remained at a relatively high level until adulthood. Male mice lacking Ccdc87 gene (Ccdc87-/-) were found to be subfertile. Approximately 20% of Ccdc87-null sperm from the testis and epididymis displayed severe abnormity of acrosome and cell nucleus. Sperm isolated from the cauda epididymides of Ccdc87-/- mice exhibited decreased initial motility but did not show any change in capacitation. Additionally, Ccdc87 disruption led to the impotency of sperm spontaneous and progesterone-induced acrosome reaction. Moreover, in vitro fertilization assays indicated that the fertilizing capacity of Ccdc87-/- sperm was significantly reduced. Taken together, these findings provide a new clue to understand the genetic causes of male infertility.

摘要

近年来,男性不育已成为一个日益普遍的健康问题。除了环境因素、营养、生活方式和性传播疾病外,遗传缺陷也是男性不育的重要原因。许多基因已被证明与男性不育有关。然而,一些功能性基因在不育症中的作用,特别是那些在生殖系统中特异性表达的基因,仍有待阐明。在这里,我们证明了睾丸特异性基因卷曲螺旋域包含 87 号(Ccdc87)对于男性生育能力至关重要。逆转录聚合酶链反应和 Western blot 分析显示,Ccdc87 mRNA 和蛋白仅在小鼠睾丸中表达。Ccdc87 表达首先出现在出生后第 14 天,并在成年期保持相对较高的水平。缺乏 Ccdc87 基因的雄性小鼠(Ccdc87-/-)表现为生育力降低。大约 20%的来自睾丸和附睾的 Ccdc87 缺失精子表现出严重的顶体和细胞核异常。从 Ccdc87-/-小鼠的附睾尾中分离出的精子初始运动能力下降,但在获能方面没有任何变化。此外,Ccdc87 缺失导致精子自发性和孕酮诱导的顶体反应的无能。此外,体外受精实验表明,Ccdc87-/-精子的受精能力显著降低。总之,这些发现为理解男性不育的遗传原因提供了新的线索。

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