The First Affiliated Hospital of USTC, National Laboratory for Physical Sciences At Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
Department of Biological Sciences, International Islamic University, Sector H10, Islamabad, 44000, Pakistan.
Mamm Genome. 2021 Oct;32(5):364-370. doi: 10.1007/s00335-021-09879-z. Epub 2021 Jun 2.
Several genes have been reported to be involved in spermatogenesis but their functional importance in male fertility is yet needed to be elucidated. Therefore, in current research, we focused to explore the in vivo role of evolutionary conserved and testis-specifically expressed, C4orf46, gene in male mouse fertility and spermatogenesis. The expression profile of C4orf46 is specific to testes and expressed in testes from 7 days of postpartum to onward. Thus, we generated the C4orf46 knockout mice by utilizing CRISPR/Cas9 genome editing technology and examined gene function in spermatogenesis and fertility. Surprisingly, C4orf46 knockout mice were completely fertile, displayed normal testes morphology, however, higher sperm contents were observed in knockout mice compared to wild type (WT) littermates. Subsequently, intact testis histology and architecture of seminiferous tubules were observed in C4orf46 knockout and WT mice. Similarly, sperm morphology and swimming velocity of C4orf46 knockout mice were comparable with the WT littermates. Furthermore, all type of germ cells ranging from spermatogonia to mature spermatozoa were observed in the testes and epididymis sections of C4orf46 knockout mice suggesting that disruption of C4orf46 did not impact spermatogenesis. Moreover, meiotic prophase I progression was normal, and each type of cell population was comparable between knockout and WT mice. Overall, finding from this research indicates that C4orf46 is not an essential gene for fertility in mice. This study will help researchers to avoid the repetition and duplication of efforts, and to explore the genes that are indispensable for spermatogenesis and male fertility.
一些基因已被报道与精子发生有关，但它们在男性生育力中的功能重要性仍有待阐明。因此，在当前的研究中，我们专注于探索进化保守且在睾丸中特异性表达的 C4orf46 基因在雄性小鼠生育力和精子发生中的体内作用。C4orf46 的表达谱特异性地存在于睾丸中，并且在产后 7 天的睾丸中表达。因此，我们利用 CRISPR/Cas9 基因组编辑技术生成了 C4orf46 敲除小鼠，并在精子发生和生育力方面检查了基因功能。令人惊讶的是，C4orf46 敲除小鼠完全具有生育能力，睾丸形态正常，但与野生型（WT）同窝仔相比，敲除小鼠的精子含量更高。随后，在 C4orf46 敲除和 WT 小鼠中观察到完整的睾丸组织学和生精小管结构。同样，C4orf46 敲除小鼠的精子形态和游动速度与 WT 同窝仔相当。此外，在 C4orf46 敲除小鼠的睾丸和附睾切片中观察到各种类型的生殖细胞，从精原细胞到成熟精子。这表明 C4orf46 的破坏不会影响精子发生。此外，减数分裂前期 I 的进展正常，并且在敲除和 WT 小鼠之间，每种细胞群的比例都相当。总的来说，这项研究的结果表明，C4orf46 不是小鼠生育力所必需的基因。这项研究将帮助研究人员避免重复和重复努力，并探索对精子发生和男性生育力必不可少的基因。
