Using mouse embryonic stem cells, researchers reconstituted ovarian follicle structures and used them to mature primordial germ cells into fully functional oocytes in vitro, which ultimately produced viable mouse offspring, according to a new report. The ability to generate and assemble the critical components necessary for oogenesis in the laboratory provides a model system to study the later events of oogenesis, which may have implications for assisted reproductive technologies. Coaxing germ cell precursors into functionally mature reproductive cells is a key aspect of in vitro gametogenesis and a major challenge in the study of reproductive biology. Successful methods have been developed to generate functional oocytes from mouse pluripotent stem cell-derived primordial germ cell-like cells (PGCLCs) in vitro. However, these cells require a somatic environment in which to develop into fully functional reproductive cells. In mammalian species, oocytes grow and mature in the ovarian follicle, a specialized fluid-filled sac that provides the signals needed for meiosis and germ cell growth. Takashi Yoshino and colleagues report a culture system that recreates this tissue environment by inducing female mouse embryonic stem cells to differentiate into functional fetal ovarian somatic cell-like cells (FOSLCs). When FOSLCs were combined with PGCLCs derived from mouse embryonic stem cells, the PGCLCs developed into viable oocytes within the reconstituted ovarian follicle structures, which could be fertilized and resulted in live, fertile offspring. "This technical breakthrough of Yoshino et al. holds enormous potential for germ cell research," write Lin Yang and Huck-Hui Ng in a related Perspective. "It allows for fully defined derivation of FOSLCs with substantial improvements in yield and without the need for genetic manipulations."