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哺乳动物精子发生过程中的核膜动力学:对男性生育能力的新认识。

Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility.

机构信息

Department of Medical Sciences, Neuroscience and Signalling Laboratory, Institute for Biomedicine (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal.

The Discovery CTR, University of Aveiro Campus, 3810-193 Aveiro, Portugal.

出版信息

Biol Rev Camb Philos Soc. 2019 Aug;94(4):1195-1219. doi: 10.1111/brv.12498. Epub 2019 Jan 31.

DOI:10.1111/brv.12498
PMID:30701647
Abstract

The production of highly specialized spermatozoa from undifferentiated spermatogonia is a strictly organized and programmed process requiring extensive restructuring of the entire cell. One of the most remarkable cellular transformations accompanying the various phases of spermatogenesis is the profound remodelling of the nuclear architecture, in which the nuclear envelope (NE) seems to be crucially involved. In recent years, several proteins from the distinct layers forming the NE (i.e. the inner and outer nuclear membranes as well as the nuclear lamina) have been associated with meiosis and/or spermiogenesis in different mammalian species. Among these are A- and B-type lamins, Dpy-19-like protein 2 (DPY19L2), lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), LAP2/emerin/MAN1 (LEM) domain-containing proteins, spermatogenesis-associated 46 (SPATA46) and diverse elements of the linker of nucleoskeleton and cytoskeleton (LINC) complex, namely Sad-1/UNC-84 homology (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain-containing proteins. Herein, we summarize the current state of the art on the cellular and subcellular distribution of NE proteins expressed during mammalian spermatogenesis, and discuss the latest research developments regarding their testis-specific functions. This review provides a comprehensive and innovative overview of the NE network as a regulatory platform and as an essential determinant of efficient meiotic chromosome recombination as well as spermiogenesis-associated nuclear remodelling and differentiation in mammalian male germline cells. Thus, this review provides important novel insights on the biological relevance of NE proteins for male fertility.

摘要

从未分化的精原细胞中产生高度特化的精子是一个严格组织和程序化的过程,需要对整个细胞进行广泛的重构。伴随着精子发生的各个阶段,最显著的细胞转化之一是核结构的深刻重塑,其中核膜(NE)似乎起着至关重要的作用。近年来,来自形成 NE 的不同层的几种蛋白质(即内、外核膜以及核层)与不同哺乳动物物种的减数分裂和/或精子发生有关。其中包括 A 型和 B 型核纤层蛋白、Dpy-19 样蛋白 2(DPY19L2)、核纤层蛋白受体(LBR)、层粘连蛋白相关多肽 1(LAP1)、LAP2/emerin/MAN1(LEM)结构域包含蛋白、精子发生相关 46(SPATA46)和连接核骨架和细胞骨架(LINC)复合物的不同元件,即 Sad-1/UNC-84 同源(SUN)和 Klarsicht/ANC-1/Syne-1 同源(KASH)结构域包含蛋白。本文总结了哺乳动物精子发生过程中表达的 NE 蛋白的细胞和亚细胞分布的最新研究进展,并讨论了其睾丸特异性功能的最新研究进展。该综述提供了一个全面而创新的 NE 网络作为调节平台的概述,以及作为减数分裂染色体重组以及哺乳动物雄性生殖细胞系中精子发生相关核重塑和分化的有效决定因素的重要性。因此,该综述提供了关于 NE 蛋白对男性生育力的生物学相关性的重要新见解。

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