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减数分裂和圆形精子细胞的形成在小鼠中不需要中心粒复制。

Meiotic divisions and round spermatid formation do not require centriole duplication in mice.

作者信息

Skinner Marnie W, Nhan Paula B, Simington Carter J, Jordan Philip W

机构信息

Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.

出版信息

PLoS Genet. 2025 Apr 28;21(4):e1011698. doi: 10.1371/journal.pgen.1011698. eCollection 2025 Apr.

Abstract

Centrosomes, composed of centrioles and pericentriolar matrix proteins, are traditionally viewed as essential microtubule-organizing centers (MTOCs) that facilitate bipolar spindle formation and chromosome segregation during spermatogenesis. In this study, we investigated the role of centrioles in male germ cell development by using a murine conditional knockout (cKO) of Sas4, a critical component of centriole biogenesis. We found that while centriole duplication was impaired in Sas4 cKO spermatocytes, these cells were still capable of progressing through meiosis I and II. Chromosome segregation was able to proceed through the formation of a non-centrosomal MTOC, indicating that centrioles are not required for meiotic divisions. However, spermatids that inherited fewer than two centrioles exhibited severe defects in spermiogenesis, including improper manchette formation, constricted perinuclear rings, disrupted acrosome morphology, and failure to form flagella. Consequently, Sas4 cKO males were infertile due to the absence of functional spermatozoa. Our findings demonstrate that while centrioles are dispensable for meiosis in male germ cells, they are essential for spermiogenesis and sperm maturation. This work provides key insights into the role of centrosomes in male fertility and may have implications for understanding certain conditions of male infertility associated with centriole defects.

摘要

中心体由中心粒和中心粒外周基质蛋白组成,传统上被视为重要的微管组织中心(MTOC),在精子发生过程中促进双极纺锤体形成和染色体分离。在本研究中,我们通过对中心粒生物发生的关键成分Sas4进行小鼠条件性敲除(cKO),研究了中心粒在雄性生殖细胞发育中的作用。我们发现,虽然Sas4 cKO精母细胞中的中心粒复制受损,但这些细胞仍能完成减数分裂I和II。染色体分离能够通过非中心体MTOC的形成进行,这表明减数分裂不需要中心粒。然而,继承少于两个中心粒的精子细胞在精子形成过程中表现出严重缺陷,包括不正确的袖套形成、核周环收缩、顶体形态破坏以及无法形成鞭毛。因此,由于缺乏功能性精子,Sas4 cKO雄性不育。我们的研究结果表明,虽然中心粒在雄性生殖细胞减数分裂中是可有可无的,但它们对精子形成和精子成熟至关重要。这项工作为中心体在男性生育中的作用提供了关键见解,并可能对理解某些与中心粒缺陷相关的男性不育症有启示。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/726a/12064039/6294082b02ba/pgen.1011698.g001.jpg

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