Reconstitution of germ cell and gonadal development for in vitro gamete production

Germ cell formation involves a unique developmental trajectory in which diploid pluripotent cells are transformed into haploid gametes through a series of tightly regulated processes. This trajectory encompasses fundamental biological events, including extensive epigenetic remodeling, sexual fate determination, and meiotic division. Understanding the molecular and cellular mechanisms governing these processes is a fundamental challenge in reproductive biology and medicine, yet many aspects remain elusive. One long-standing strategy to overcome this limitation has been the establishment of in vitro gametogenesis that recapitulates germ cell development under defined culture conditions. In recent years, advances in stem cell biology have dramatically accelerated the development of such systems, opening new experimental platforms to dissect germ cell development. Beyond their value as research tools, these technologies also hold potential as alternative sources of gametes for animal reproduction and, perhaps, for human applications. In this review, we discuss the historical evolution of in vitro gametogenesis, highlight recent progress in the field, and outline the remaining technical and conceptual challenges.