Saitou Mitinori, Nagano Masahiro, Mizuta Ken
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.
Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nat Rev Mol Cell Biol. 2025 Sep 16. doi: 10.1038/s41580-025-00893-6.
Human germ cells are the foundation of human reproduction and development, ensuring heredity and contributing to genetic diversity. Accordingly, their anomalies lead to critical diseases, including infertility. Recent advances in genomics and stem cell-based in vitro gametogenesis research have expanded our knowledge of how human germ cells are specified and differentiate during embryonic and fetal development, elucidating evolutionarily distinctive as well as conserved properties of human germ cell development. Here, based on the evidence from both in vivo and in vitro studies, we provide an integrated review of the progress in our understanding of human embryonic and fetal germ cell development, encompassing germ cell specification, epigenetic reprogramming and sex-specific germ cell development. Knowledge of the mechanisms of human germ cell development will enable its in vitro reconstitution, which in turn will serve as a foundation for innovative medical strategies to prevent germ cell-related diseases, including infertility.
人类生殖细胞是人类生殖和发育的基础，确保遗传并促进遗传多样性。因此，它们的异常会导致包括不孕症在内的严重疾病。基因组学和基于干细胞的体外配子发生研究的最新进展，扩展了我们对人类生殖细胞在胚胎和胎儿发育过程中如何被指定和分化的认识，阐明了人类生殖细胞发育在进化上独特以及保守的特性。在此，基于体内和体外研究的证据，我们对人类胚胎和胎儿生殖细胞发育的理解进展进行了综合综述，涵盖生殖细胞的指定、表观遗传重编程和性别特异性生殖细胞发育。了解人类生殖细胞发育的机制将使其能够在体外重建，这反过来又将为预防包括不孕症在内的生殖细胞相关疾病的创新医学策略奠定基础。
