ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis.

ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis.
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DOI:
10.1038/s41467-023-37735-y
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发表时间:
2023-04-17
影响因子:
16.6
通讯作者:
Oatley, Jon M.
Oatley, Jon M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Giassetti, Mariana I.;Miao, Deqiang;Law, Nathan C.;Oatley, Melissa J.;Park, Julie;Robinson, LeeLa D.;Maddison, Lisette A.;Bernhardt, Miranda L.;Oatley, Jon M.

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在有性生殖中,精子提供了创造后代所需的一半基因组物质,但其形成所必需的核心分子机制尚不明确。本文中,α-抑制素分子arrestin-domain containing 5 (ARRDC5)被确定为哺乳动物精子发生的重要调控因子。多物种睾丸组织转录组分析表明,在小鼠、猪、牛和人类中,Arrdc5的表达是睾丸富集的,如果不是特异性的。敲除小鼠体内的Arrdc5会导致雄性特异性不育,原因是精子数量少,不能运动,畸形。精子发生是精子发生的最后阶段,圆形精子细胞转变为精子,在Arrdc5缺陷小鼠的睾丸中是有缺陷的。此外,在Arrdc5基因敲除中,附睾精子不能使卵母细胞获得能力并使其受精。这些发现证实了ARRDC5是哺乳动物精子发生的重要调节因子。考虑到阻滞蛋白分子作为细胞信号和泛素化的调节剂的作用,ARRDC5是一个潜在的男性避孕靶点。雄性生物每天产生大量精子,过程中的缺陷导致不育。他们发现含有阻滞蛋白结构域5 (ARRDC5)是哺乳动物精子发生所需的睾丸特异性分子。
In sexual reproduction, sperm contribute half the genomic material required for creation of offspring yet core molecular mechanisms essential for their formation are undefined. Here, the α-arrestin molecule arrestin-domain containing 5 (ARRDC5) is identified as an essential regulator of mammalian spermatogenesis. Multispecies testicular tissue transcriptome profiling indicates that expression of Arrdc5 is testis enriched, if not specific, in mice, pigs, cattle, and humans. Knockout of Arrdc5 in mice leads to male specific sterility due to production of low numbers of sperm that are immotile and malformed. Spermiogenesis, the final phase of spermatogenesis when round spermatids transform to spermatozoa, is defective in testes of Arrdc5 deficient mice. Also, epididymal sperm in Arrdc5 knockouts are unable to capacitate and fertilize oocytes. These findings establish ARRDC5 as an essential regulator of mammalian spermatogenesis. Considering the role of arrestin molecules as modulators of cellular signaling and ubiquitination, ARRDC5 is a potential male contraceptive target. Male organisms produce huge numbers of sperm each day, with defects in the process resulting infertility. Here they show that arrestin domain-containing 5 (ARRDC5) is a testis-specific molecule required for mammalian spermatogenesis.
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