open access

https://hdl.handle.net/2115/97411

Effect of introducing somatic mitochondria into an early embryo on zygotic gene activation

英語

zygotic gene activation

2025-01-15

Oxford University Press

Biology of reproduction

112(4)

614-627

Unlike differentiated somatic cells, which possess elongated mitochondria, undifferentiated cells, such as those of preimplantation embryos, possess round, immature mitochondria. Mitochondrial morphology changes dynamically during cell differentiation in a process called mitochondrial maturation. The significance of the alignment between cell differentiation and mitochondrial maturity in preimplantation development remains unclear. In this study, we analyzed mouse embryos into which liver-derived somatic mitochondria were introduced (SM-embryos). Most SM-embryos were arrested at the two-cell stage. Some of the introduced somatic mitochondria became round, while others remained elongated and large. RNA-sequencing revealed a disruption of both minor and major zygotic gene activation (ZGA) in SM-embryos. Minor ZGA did not terminate before major ZGA, and the onset of major ZGA was inhibited, as shown by histone modification analyses of histone H3 lysine 4 trimethylation and histone H3 lysine 27 acetylation. Further analysis of metabolites involved in histone modification regulation in SM-embryos showed a significantly lower NAD+/NADH ratio in SM-embryos than in control embryos. Additionally, the mitochondrial membrane potential, an indicator of mitochondrial function, was lower in SM-embryos than in control embryos. Our results demonstrated that introducing somatic mitochondria into an embryo induces mitochondrial dysfunction, thereby disrupting metabolite production, leading to a disruption in ZGA and inducing developmental arrest. Our findings reveal that the alignment between cell differentiation and mitochondrial maturity is essential for early embryonic development. Sentence: Mismatch between cell differentiation and mitochondrial maturity prevents transition from minor to major ZGA in mouse embryos.

学術雑誌論文

Accepted Manuscript

This is a pre-copyedited, author-produced version of an article accepted for publication in Biology of reproduction following peer review. The version of record Biology of Reproduction, Volume 112, Issue 4, April 2025, Pages 614–627, is available online at: https://doi.org/10.1093/biolre/ioaf010.

0006-3363