SummaryMeiosis is a highly conserved process, and is responsible for the production of haploid gametes and generation of genetic diversity. We previously identified the transferrin receptor (TFRC) in the proteome profile of mice neonatal testes, indicating the involvement of the TFRC in meiosis. However, the exact molecular role of the TFRC in meiosis remains unclear. In this study, we aimed to determine the function of the TFRC in neonatal testicular development by TFRC knockdown using the testis culture platform. Our results showed high TFRC expression in 2-week testes, corresponding to the first meiotic division. Targeting TFRC using morpholino oligonucleotides resulted in clear spermatocyte apoptosis. In addition, we used the chromosomal spread technique to show that a deficiency of TFRC caused the accumulation of leptotene and zygotene spermatocytes, and a decrease of pachytene spermatocytes, indicating early meiotic arrest. Moreover, the chromosomes of TFRC-deficient pachytene spermatocytes displayed sustained γH2AX association, as well as SYCP1/SYCP3 dissociation beyond the sex body. Therefore, our results demonstrated that the TFRC is essential for the progression of spermatocyte meiosis, particularly for DNA double-stranded break repair and chromosomal synapsis.

中文翻译：

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转铁蛋白受体 (TFRC) 对小鼠精子发生过程中的减数分裂进程至关重要

摘要减数分裂是一个高度保守的过程，负责单倍体配子的产生和遗传多样性的产生。我们之前在小鼠新生儿睾丸的蛋白质组谱中发现了转铁蛋白受体 (TFRC)，表明 TFRC 参与了减数分裂。然而，TFRC 在减数分裂中的确切分子作用仍不清楚。在本研究中，我们旨在使用睾丸培养平台通过 TFRC 敲低来确定 TFRC 在新生儿睾丸发育中的功能。我们的结果显示 2 周睾丸中的高 TFRC 表达，对应于第一次减数分裂。使用吗啉代寡核苷酸靶向 TFRC 导致明显的精母细胞凋亡。此外，我们使用染色体扩散技术表明，TFRC 的缺乏导致细线期和合子期精母细胞的积累，以及粗线期精母细胞的减少，表明早期减数分裂停滞。此外，缺乏 TFRC 的粗线期精母细胞的染色体显示出持续的 γH2AX 结合，以及 SYCP1/SYCP3 在性体之外的解离。因此，我们的研究结果表明，TFRC 对于精母细胞减数分裂的进展至关重要，特别是对于 DNA 双链断裂修复和染色体突触。