Molecular Regulation of Primordial Germ Cell Specification and Implications for In Vitro Gametogenesis

Primordial germ cells (PGCs) are the embryonic precursors of gametes, essential for transmitting genetic and epigenetic information across generations. However, PGC specification occurs within a narrow developmental window and involves only a small number of cells, making it difficult to study in vivo. In vitro models using pluripotent stem cells have enabled the generation of primordial germ cell-like cells, but these systems often rely on exogenous signaling and exhibit variability in efficiency and epigenetic fidelity. In this review, we synthesize current understanding of PGC specification in mouse and human systems, emphasizing the integration of signaling pathways, transcriptional networks, epigenetic reprogramming, and metabolic regulation. Canonical regulators, including PRDM1, PRDM14, TFAP2C, and SOX17, function within a broader, interconnected network that establishes for PGC competence. Understanding these interactions will be crucial for advancing in vitro gametogenesis and improving mammalian reproduction.