Induced pluripotent stem cell (iPSC)-based in vitro gametogenesis (IVG) provides a possible route from cryobanked or collected somatic cells to functional gametes and, ultimately, offspring. However, full offspring-level proof of concept has so far been largely demonstrated in mice. In livestock, non-human primates and threatened species, iPSC-based IVG remains prospective, with most studies restricted to derivation of pluripotent cells, specification of primordial germ cell-like cells or partial germline development. If successfully developed, this technology could increase the representation of founders in threatened populations, recover genetic contributions from non-reproductive or deceased animals, and potentially support shorter generation intervals and targeted trait introgression in livestock. Here, we critically evaluate the biological and translational requirements for iPSC-based IVG. These include reprogramming quality, germline specification, epigenetic reprogramming, imprint erasure, meiosis, sex-specific gonadal niches, gamete maturation, embryo development and long-term offspring assessment. iPSC-based IVG should be integrated with cryobanking, population-genetic management, assisted reproduction, animal welfare and habitat recovery for conservation. In livestock, applications include management of genetic diversity, recovery of rare breeds, shorter generation intervals, and targeted trait introgression. The current evidence shows that it is research and protocol development, not commercial deployment. A stage-gated validation framework and a cross-species roadmap are proposed. Reproductive application should require evidence from genomics, epigenomics, cytology, function, development, and multiple generations.
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Khan et al. (2026) studied this question.
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