The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
Biomolecules. 2024 Jul 12;14(7):840. doi: 10.3390/biom14070840.
In studying the molecular underpinning of spermatogenesis, we expect to understand the fundamental biological processes better and potentially identify genes that may lead to novel diagnostic and therapeutic strategies toward precision medicine in male infertility. In this review, we emphasized our perspective that the path forward necessitates integrative studies that rely on complementary approaches and types of data. To comprehensively analyze spermatogenesis, this review proposes four axes of integration. First, spanning the analysis of spermatogenesis in the healthy state alongside pathologies. Second, the experimental analysis of model systems (in which we can deploy treatments and perturbations) alongside human data. Third, the phenotype is measured alongside its underlying molecular profiles using known markers augmented with unbiased profiles. Finally, the testicular cells are studied as ecosystems, analyzing the germ cells alongside the states observed in the supporting somatic cells. Recently, the study of spermatogenesis has been advancing using single-cell RNA sequencing, where scientists have uncovered the unique stages of germ cell development in mice, revealing new regulators of spermatogenesis and previously unknown cell subtypes in the testis. An in-depth analysis of meiotic and postmeiotic stages led to the discovery of marker genes for spermatogonia, Sertoli and Leydig cells and further elucidated all the other germline and somatic cells in the testis microenvironment in normal and pathogenic conditions. The outcome of an integrative analysis of spermatogenesis using advanced molecular profiling technologies such as scRNA-seq has already propelled our biological understanding, with additional studies expected to have clinical implications for the study of male fertility. By uncovering new genes and pathways involved in abnormal spermatogenesis, we may gain insights into subfertility or sterility.
在研究精子发生的分子基础时，我们期望更好地理解基本的生物学过程，并有可能鉴定出可能导致男性不育症精准医学新的诊断和治疗策略的基因。在这篇综述中，我们强调了我们的观点，即前进的道路需要依靠互补的方法和类型的数据进行综合研究。为了全面分析精子发生，本综述提出了四个整合轴。首先，跨越健康状态和病理学的精子发生分析。其次，在模型系统中进行实验分析（我们可以在其中部署治疗和干扰）以及人类数据。第三，使用已知标记物并增加无偏标记物来测量表型及其潜在的分子谱。最后，将睾丸细胞作为生态系统进行研究，分析生殖细胞及其支持体细胞中观察到的状态。最近，使用单细胞 RNA 测序技术，精子发生的研究取得了进展，科学家们在小鼠中揭示了生殖细胞发育的独特阶段，发现了精子发生的新调节因子和睾丸中以前未知的细胞亚型。对减数分裂和减数分裂后阶段的深入分析导致了精原细胞、Sertoli 和 Leydig 细胞的标记基因的发现，并进一步阐明了正常和病理条件下睾丸微环境中的所有其他生殖细胞和体细胞。使用 scRNA-seq 等先进分子分析技术对精子发生进行综合分析的结果已经推动了我们的生物学理解，预计进一步的研究将对男性生育能力的研究具有临床意义。通过揭示异常精子发生中涉及的新基因和途径，我们可能会深入了解生育能力低下或不育的原因。
