Raw data for all quantified values in this study.
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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.
中心体(Centrosomes)由中心粒(centrioles)和中心粒周基质蛋白(pericentriolar matrix proteins)组成,传统上被认为是不可或缺的微管组织中心(microtubule-organizing centers, MTOCs),可在精子发生过程中促进双极纺锤体形成与染色体分离。本研究通过构建靶向Sas4(中心粒发生的关键组分)的小鼠条件性敲除(conditional knockout, cKO)模型,探究了中心粒在雄性生殖细胞发育中的作用。研究发现,尽管Sas4条件性敲除的精母细胞(spermatocytes)中中心粒复制受到阻碍,但此类细胞仍可顺利完成减数第一次分裂与减数第二次分裂。染色体分离可通过非中心体微管组织中心的形成顺利进行,这表明中心粒并非减数分裂所必需。然而,继承不足两个中心粒的精子细胞(spermatids)在精子形成(spermiogenesis)过程中出现严重缺陷,具体表现为曼切特结构(manchette)形成异常、核周环收缩、顶体(acrosome)形态紊乱以及鞭毛(flagella)无法形成。因此,Sas4条件性敲除的雄性小鼠因缺乏功能性精子而不育。本研究结果证实,尽管中心粒对于雄性生殖细胞的减数分裂并非必需,但它们对于精子形成与精子成熟至关重要。本工作为阐明中心体在雄性生育能力中的作用提供了关键见解,或可为理解部分与中心粒缺陷相关的男性不育症(male infertility)提供参考依据。
创建时间:
2025-04-28



