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Recent advances have enabled the generation of oocytes from pluripotent stem cells in vitro. However, these cells require a somatic environment to develop fully as reproductive cells. Yoshino et al. applied what is known about differentiation processes in vivo to determine a culture condition to differentiate embryonic stem cells into gonadal somatic cell–like cells (see the Perspective by Yang and Ng). When the embryonic stem cell–generated ovarian gonadal tissue was combined with early primordial germ cells or in vitro–derived primordial germ cell–like cells, germ cells developed into viable oocytes within the reconstituted follicles that could be fertilized and result in viable offspring. This system enables an alternative method for mouse gamete production and advances our understanding of mammalian reproduction and development.
Germ cells develop in a specific environment in the reproductive organs. Throughout oogenesis, oocytes are encapsulated by somatic cells in follicle structures that provide numerous signals and components essential for key events in oocyte development, such as meiosis and growth. The interaction between the oocyte and the somatic follicular cells is regulated in a stage-dependent manner. Recently, in vitro gametogenesis, reconstitution of germ cell development in culture using pluripotent stem cells, has been developed in mammalian species, including mice and humans. In mice, functional oocytes can be produced from pluripotent stem cell–derived primordial germ cell–like cells (PGCLCs) by reaggregation with embryonic ovarian somatic cells at embryonic day 12.5. Therefore, in vitro gametogenesis is expected to be an innovative means of producing a robust number of oocytes in culture. This should be particularly useful for application to humans and endangered animals. However, the in vitro reconstitution of germ cell development is highly dependent on the somatic cell environment provided by embryonic ovarian tissue, which is difficult to obtain from mammalian species. Here, we provide a model system that reconstitutes the ovarian somatic cell environment using mouse pluripotent stem cells.