Epigenetic Reprogramming and Zygotic Genome Activation in Human Preimplantation Development: Mechanisms, Models, and Translational Prospects

Abstract

ABSTRACT Purpose Early human embryogenesis unfolds through a tightly coupled sequence of events—clearance of maternal transcripts, remodeling of parental chromatin, zygotic genome activation (ZGA), lineage segregation, implantation, and post‐implantation patterning—accompanied by epigenetic reprogramming, including X‐chromosome dosage compensation around the time of implantation. This review aims to synthesize recent advances in understanding this developmental program and to consider their implications for reproductive medicine. Methods I review recent literature on human early embryogenesis, with particular emphasis on findings enabled by single‐cell genomics and stem‐cell‐based embryo modeling, and integrate these insights to identify human‐specific features of early development. Results These approaches have made previously inaccessible aspects of human early embryogenesis experimentally tractable, revealing molecular and epigenetic features that distinguish human development from that of model organisms, including species‐specific dynamics of ZGA, maternal transcript clearance, chromatin reprogramming, and X‐chromosome dosage compensation. Conclusions Advances in single‐cell genomics and embryo modeling are transforming our understanding of human early embryogenesis. Building on these insights, while recognizing their current limitations, I propose a vision for improving reproductive medicine, including the potential for next‐generation embryo selection strategies.