From Oocytes to Early Embryos: Specialized Cell Division Strategies for Maintaining Genome Stability

Hirohisa Kyogoku

Associate Professor, Graduate School of Agricultural Science, Kobe University

Early mammalian development is characterized by a series of rapid cell divisions that occur without accompanying cell growth. Oocytes and zygotes possess exceptionally large cytoplasmic volumes, containing abundant maternal factors that support early embryogenesis. These unique cellular environments raise a fundamental question: do oocytes and early embryos employ the same mechanisms of cell division and genome maintenance as somatic cells?

In this seminar, I will present our recent studies revealing stage-specific strategies that safeguard genome integrity during early mammalian development. First, I will describe how the exceptionally large cytoplasmic volume of oocytes compromises spindle stability and spindle assembly checkpoint (SAC) efficiency, thereby increasing the risk of chromosome segregation errors. Next, I will introduce our recent finding that the two parental pronuclei in the zygote compete for limiting cytoplasmic factors required for nuclear assembly, thereby regulating pronuclear size, epigenetic state, and developmental potential. Finally, I will discuss how the DNA replication timing program is progressively established during preimplantation development, and how its emergence is closely associated with replication stress and genome instability.

Together, these studies demonstrate that oocytes and early embryos employ specialized cell division strategies that differ fundamentally from those of somatic cells. By integrating live-cell imaging with single-cell genomic and epigenomic approaches, our work provides new insights into the mechanisms that preserve genome integrity during the earliest stages of mammalian life.

Reference

Cytoplasmic competition between separate parental pronuclei in zygotes.

Kyogoku H, Tarama M, Matsuwaka M, Mishina T, Harada A, Nakagawa R, Kumon M, Shimizu Y, Ohkawa Y, Shibata T, Inoue A, Kitajima TS.

Nature. 2026, 654(8117):189-197

Embryonic genome instability upon DNA replication timing program emergence.

Takahashi S, Kyogoku H, Hayakawa T, Miura H, Oji A, Kondo Y, Takebayashi SI, Kitajima TS, Hiratani I.

Nature. 2024, 633(8030):686-694.

Large Cytoplasm Is Linked to the Error-Prone Nature of Oocytes.

Kyogoku H, Kitajima TS.

Dev Cell. 2017, 8;41(3):287-298.e4.