Primordial germ cells (PGCs) are the direct progenitors of male and female gametes in higher animals. In vertebrates, PGCs are initially specified during gastrulation, after which they exit their resident tissue, migrate as single cells across different tissue contexts towards a signaling center of mesodermal cells where they associate with somatic cells to form sex-specific reproductive organs. During their migration, PGCs undergo extensive epigenetic remodeling as well as further differentiation into a mature germline fate. However, we have limited understanding of the molecular and physical cues driving PGC migration and maturation. We propose that the physical architecture of embryos presents a highly confining environment during PGC migration, requiring the cells to undergo drastic nuclear deformations to move through tissues. Nuclear deformation, previously shown to induce epigenetic changes, may act as a mechanical signal for PGC epigenetic remodeling, ultimately guiding maturation of PGCs. We further propose that histone remodeling during PGC migration is essential to protect the germline genome from damage during migration through confined environments. To examine the extent of confinement imposed by embryonic tissues, we used zebrafish embryos to characterize nuclear morphology in migrating PGCs. We found that zebrafish PGCs migrate through gaps between tissue layers as well as within the tissue bulk. During migration, they exhibited drastic deformation of the nucleus, with nuclei showing a ruffled appearance and extensive folding. This indicates that surrounding cells and tissues exert significant confining forces on PGC nuclei. To explore confinement-driven fate determination in human PGCs, we developed a microchannel-based device to recapitulate physiological confinement. Primordial germ-like cells (PGLCs) were derived from embryonic stem cells in a monolayer and introduced to microchannels of varying dimensions. We observed that PGLCs migrated through confining (30 and 50 µm2) as well as non-confining microchannels (100 µm2) without any chemotactic signals. Going forward, we hope to utilize this system, combined with in vivo studies in zebrafish to gain a comprehensive understanding of the migratory environment of germ cells and the role it plays in maturation of the germline.