Elevated Id2 expression causes defective meiosis and spermatogenesis in mice

• Published in: Developmental dynamics 2024-06, Vol.253 (6), p.593-605
• Main Authors: He, Zhen, Yan, Rong‐Ge, Shang, Qin‐Bang, Yang, Qi‐En
• Format: Article
• Language: English
• Subjects: Ablation; Abnormalities; Cell fate; Defects; Gametocytes; Gene expression; Germ cells; Id protein; ID proteins; Id1 protein; Id2 protein; Meiosis; MLH1 protein; Pachytene; Proteins; recombination; Spermatocytes; Spermatogenesis; Spermatogonia; Spermiogenesis; Stem cells; Testes; Transcriptomes; Zygotene
• ISSN: 1058-8388; 1097-0177; 1097-0177
• DOI: 10.1002/dvdy.676

Background Inhibitors of DNA binding (ID) proteins mainly inhibit gene expression and regulate cell fate decisions by interacting with E‐proteins. All four ID proteins (ID1–4) are present in the testis, and ID4 has a particularly important role in spermatogonial stem cell fate determination. Several lines of evidence indicate that ID proteins are involved in meiosis; however, functional experiments have not been conducted to validate this observation. Results In this study, we report that ID2 is enriched in spermatocytes and that forced ID2 expression in germ cells causes defects in spermatogenesis. A detailed analysis demonstrated that Id2 overexpression (Id2 OE) decreased the total number of spermatogonia and changed the dynamics of meiosis progression. Specifically, spermatocytes were enriched in the zygotene stage, and the proportion of pachytene spermatocytes was significantly decreased, indicating defects in the zygotene–pachytene transition. The number of MLH1‐positive foci per cell was decreased in pachytene spermatocytes from Id2 OE testes, suggesting abnormalities in recombination. Transcriptome analysis revealed that forced Id2 expression changed the expression of a list of genes mainly associated with meiosis and spermatid development. Conclusions ID2 protein is expressed in spermatocytes, and its genetic ablation in the germline does not affect spermatogenesis, likely due to genetic compensation of its family members. However, forced Id2 expression changes meiosis progression and causes defects in spermiogenesis. These data provide important evidence that ID proteins play pivotal roles in male meiosis and spermatid development. Key Findings ID proteins; Spermatogenesis; Recombination; Meiosis; Pachytene.