Outside the box: comparative stem cell insights for fertility biotechnology and conservation

Leveraging comparative biology could lead to breakthrough discoveries in the development of fertility technologies while supporting conservation efforts. Here, we discuss examples and opportunities to learn from stem cell systems in nontraditional animal models, primarily from the amniote phylum, focusing on challenges and insights in the in vitro derivation of primordial germ cells and gametes, as well as the promise of gonadal stem cells. Embryo models and organoid systems provide a further opportunity to explore germ cell specification and maturation within a proxy 'in vivo' context. Additionally, stem cells enable high-throughput molecular studies to explore the mechanisms underlying fertility-related diseases. Using the international effort to derive gametes from stem cells of the Northern White Rhino as a case study, we highlight the contribution of alternative mammalian systems within the field of assisted reproductive treatments and point toward promising directions for future research. Contextualizing stem cell derivation and differentiation within a comparative species framework will be essential for harnessing the full potential of reproductive technologies for human fertility while simultaneously opening new frontiers in wildlife conservation.