The minipig as a programmable translational platform for experimental oncofertility

Experimental oncofertility remains fragmented across models of cancer biology, treatment-associated gonadotoxicity, fertility preservation, and reproductive recovery. We propose extending the Oncopig concept into a translational platform that reconnects these states within one genetically defined, cancer-bearing host. The Oncopig provides the oncologic backbone, combining programmable cancer in an immunocompetent large-animal host with clinically scaled intervention and longitudinal sampling. High-resolution porcine genomics, CRISPR-based genome engineering, somatic-cell nuclear transfer for line generation, comparative experimental pathology, and mature reproductive biotechnology extend this architecture toward reproductive endpoints. Here, programmability refers to deliberate specification of the cancer state-genotype, cell lineage or induction strategy, and timing-whereas the reproductive phenotype is measured longitudinally rather than programmed. Distant-cancer modules can test whether cancer status modifies gonadotoxicity, while reproductive-organ modules require disease-specific alleles, appropriate cell-of-origin targeting, and pathology-led validation. Because porcine and human reproduction align in several endocrine and gonadal processes but differ in cycle organization, implantation, placentation, and pregnancy, translation should emphasize process-level endpoints rather than numerical equivalence. The platform is particularly suited to unresolved questions involving targeted therapies and immunotherapies, preservation timing, and pediatric or prepubertal patients. Porcine reproductive biotechnology provides functional endpoints from gonadal tissue and gametes to embryos and offspring. Rather than replacing rodent or human-based models, the Oncopig framework adds an integrated translational layer for questions requiring clinically scaled intervention, longitudinal physiology, and functional reproductive recovery.