The Stage of Differentiation Into Mature Gametes During Gametogenesis in Vitro

Abstract

In vitro gametogenesis (IVG) stands as a revolutionary breakthrough in reproductive biology, offering the unprecedented capability to generate functional gametes from pluripotent stem cells (PSCs). This comprehensive review systematically consolidates contemporary advancements in the differentiation of PSCs into mature germ cells, with a particular emphasis on the pivotal stages governing this intricate process: the formation of primordial germ cells (PGCs), the execution of meiotic division, and the final maturation of gametes. Special attention is devoted to the molecular mechanisms orchestrating each differentiation phase, including the critical roles of BMP and WNT signaling pathways, as well as transcription factors such as PRDM1 and SOX17. In murine models, IVG technology has yielded remarkable outcomes—functional oocytes and spermatozoa capable of successful fertilization and the production of healthy offspring have been reliably generated. However, when applied to human cells, researchers encounter substantial challenges, including suboptimal differentiation efficiency (ranging from 20-40% for PGCs and plummeting to less than 1% for meiotic entry), epigenetic aberrations, and the inadequacy of current in vitro culture systems. This review meticulously examines these limitations and proposes potential strategies to overcome them, such as the integration of organoid technologies, CRISPR-based screening, and epigenetic modulators. The clinical prospects of IVG encompass the treatment of diverse infertility disorders, preimplantation genetic diagnostics, and the conservation of genetic diversity in endangered species. Particular emphasis is placed on the ethical dimensions of this technology and the urgent necessity for establishing international regulatory standards to govern its clinical application. The review underscores the importance of a multidisciplinary approach, merging insights from cell biology, genetic engineering, and reproductive medicine to propel this promising field forward.