Across amniotes, squamates represent the only clade with highly variable parity modes, oviparity (egg-laying) and viviparity (live-birth). Despite this, relatively little is known about how oviparity and viviparity evolve at the genomic and physiological levels in squamates. Within the context of interdisciplinary medical, poultry science, and reproductive biology literature, I review the genomics and physiology of reproduction across five broad processes expected to change during transitions between parity modes—eggshell formation, embryonic retention, placentation, calcium transport, and maternal-fetal immune dynamics. This review is the first time that the maternal-fetal immune dynamics of squamates is considered in the context of modern medical literature, where embryos are no longer conceptualized as analogs to allografts. I offer alternative perspectives and holistic hypotheses on the genomic and transcriptomic drivers of parity mode transitions in squamates. Two new pathways through which early Lepidosaurs may have transitioned rapidly between oviparity and viviparity with no intermediate stages are presented. Overall, the physiology of reproduction illuminates the biological plausibility of highly labile parity modes in some squamate lineages, with constrained parity modes in others. Future research should be open to either possibility unless clade-specific biological evidence suggests otherwise. Rather than emphasizing the feasibility of transitions in either direction, I posit that oviparity and viviparity are relatively minor variations of a shared process.
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