Abstract
Male gametogenesis involves both mitotic divisions to amplify germ cell progenitors that gradually differentiate and meiotic divisions. Centrosomal regulation is essential for both types of divisions, with centrioles remaining tightly paired during the interphase. Here, we generated and characterized the phenotype of mutant mice devoid of Cep250/C-Nap1, a gene encoding for a docking protein for fibers linking centrioles, and characterized their phenotype. The Cep250 -/- mice presented with no major defects, apart from male infertility due to a reduction in the spermatogonial pool and the meiotic blockade. Spermatogonial stem cells expressing Zbtb16 were not affected, whereas the differentiating spermatogonia were vastly lost. These cells displayed abnormal γH2AX-staining, accompanied by an increase in the apoptotic rate. The few germ cells that survived at this stage, entered the meiotic prophase I and were arrested at a pachytene-like stage, likely due to synapsis defects and the unrepaired DNA double-strand breaks. In these cells, centrosomes split up precociously, with γ-tubulin foci being separated whereas these were closely associated in wild-type cells. Interestingly, this lack of cohesion was also observed in wild-type female meiocytes, likely explaining the normal fertility of Cep250 -/- female mice. Taken together, this study proposes a specific requirement of centrosome cohesion in the male germline, with a crucial role of CEP250 in both differentiating spermatogonia and meiotic spermatocytes.
Highlights
Gametogenesis displays striking sex-specific features in mammals (Teletin et al, 2017; Spiller and Bowles, 2019)
CEP250 was localized between the two γ-tubulin foci which supported its possible role in centrosome cohesion during spermatogenesis (Figure 1D)
Our data indicate that CEP250 is essential for maintaining centrosome cohesion in male germ cells
Summary
Gametogenesis displays striking sex-specific features in mammals (Teletin et al, 2017; Spiller and Bowles, 2019). Oogenesis is initiated during fetal life, with primordial germ cells rapidly initiating meiosis after a few rounds of mitotic divisions in the ovary. Spermatogenesis is a cellular differentiation process that includes several coordinated steps that lead to the production of spermatozoa (Griswold, 2015). These steps comprise proliferation and differentiation of spermatogonia, spermatocyte meiosis, and post-meiotic differentiation of spermatids. The spermatogonial stem cells can self-renew and produce undifferentiated A-type spermatogonial progenitors that are committed to spermatogenesis
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