Research Branch, Sidra Medicine, Doha, Qatar.
Weill Cornell Medicine, Doha, Qatar.
J Transl Med. 2024 May 19;22(1):473. doi: 10.1186/s12967-024-05162-2.
The study of the functional genome in mice and humans has been instrumental for describing the conserved molecular mechanisms regulating human reproductive biology, and for defining the etiologies of monogenic fertility disorders. Infertility is a reproductive disorder that includes various conditions affecting a couple's ability to achieve a healthy pregnancy. Recent advances in next-generation sequencing and CRISPR/Cas-mediated genome editing technologies have facilitated the identification and characterization of genes and mechanisms that, if affected, lead to infertility. We report established genes that regulate conserved functions in fundamental reproductive processes (e.g., sex determination, gametogenesis, and fertilization). We only cover genes the deletion of which yields comparable fertility phenotypes in both rodents and humans. In the case of newly-discovered genes, we report the studies demonstrating shared cellular and fertility phenotypes resulting from loss-of-function mutations in both species. Finally, we introduce new model systems for the study of human reproductive biology and highlight the importance of studying human consanguineous populations to discover novel monogenic causes of infertility. The rapid and continuous screening and identification of putative genetic defects coupled with an efficient functional characterization in animal models can reveal novel mechanisms of gene function in human reproductive tissues.
对小鼠和人类功能基因组的研究，对于描述调控人类生殖生物学的保守分子机制，以及定义单基因生育障碍的病因学，都具有重要作用。不孕是一种生殖障碍，包括各种影响夫妻实现健康妊娠能力的病症。新一代测序和 CRISPR/Cas 介导的基因组编辑技术的最新进展，促进了对导致不孕的基因和机制的鉴定和特征描述。我们报告了在基本生殖过程中起调节作用的已确定基因（例如性别决定、配子发生和受精）。我们只涵盖那些在啮齿动物和人类中缺失会产生类似生育表型的基因。对于新发现的基因，我们报告了在这两个物种中由于功能丧失突变而导致的共享细胞和生育表型的研究。最后，我们引入了新的人类生殖生物学研究模型系统，并强调了研究人类近亲群体以发现新的单基因不孕病因的重要性。快速和连续的筛选和鉴定潜在的遗传缺陷，加上在动物模型中的有效功能特征描述，可能揭示人类生殖组织中基因功能的新机制。
