A Murine Model Yielding Functional Sperm and Implications for Human In Vitro Gametogenesis
DOI:
https://doi.org/10.65649/e6h6sy52Keywords:
In Vitro Gametogenesis, Spermatogenesis, Pluripotent Stem Cells, Primordial Germ Cell-like Cells, Meiosis, Spermatozoa, Infertility, Epigenetics, BioethicsAbstract
The reconstitution of complete spermatogenesis in vitro remains a pivotal challenge in reproductive biology, with transformative potential for treating infertility and modeling disease. This study establishes a three-step protocol for synthetic spermatogenesis, enabling the generation of functional spermatozoa from mouse and human pluripotent stem cells (PSCs). Initially, PSCs were efficiently differentiated into primordial germ cell-like cells (PGCLCs) with appropriate epigenetic reprogramming. PGCLCs were then co-cultured with primary testicular somatic cells on a 3D scaffold, where they self-organized into seminiferous tubule-like structures. Sequential hormonal stimulation with retinoic acid, testosterone, and follicle-stimulating hormone (FSH) drove meiotic progression and haploid spermatid formation. In the mouse system, complete spermiogenesis was achieved, yielding sperm capable of fertilizing oocytes via intracytoplasmic sperm injection (ICSI) and producing healthy, fertile offspring. Human PGCLCs entered meiosis and formed haploid cells, but terminal spermiogenesis efficiency remained low. This work provides a foundational model for in vitro gametogenesis, offering new avenues for studying male reproduction and addressing absolute infertility, while highlighting critical technical and ethical considerations.
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