Depletion of oocyte dynamin-related protein 1 shows maternal-effect abnormalities in embryonic development

Deepak Adhikari, In Won Lee, Usama Al-Zubaidi, Jun Liu, Qing Hua Zhang, Wai Shan Yuen, Likun He, Yasmyn Winstanley, Hiromi Sesaki, Jeffrey R. Mann, Rebecca L. Robker, John Carroll

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12 Citations (Scopus)

Abstract

Eggs contain about 200,000 mitochondria that generate adenosine triphosphate and metabolites essential for oocyte development. Mitochondria also integrate metabolism and transcription via metabolites that regulate epigenetic modifiers, but there is no direct evidence linking oocyte mitochondrial function to the maternal epigenome and subsequent embryo development. Here, we have disrupted oocyte mitochondrial function via deletion of the mitochondrial fission factor Drp1. Fission-deficient oocytes exhibit a high frequency of failure in peri- and postimplantation development. This is associated with altered mitochondrial function, changes in the oocyte transcriptome and proteome, altered subcortical maternal complex, and a decrease in oocyte DNA methylation and H3K27me3. Transplanting pronuclei of fertilized Drp1 knockout oocytes to normal ooplasm fails to rescue embryonic lethality. We conclude that mitochondrial function plays a role in establishing the maternal epigenome, with serious consequences for embryo development.

Original languageEnglish
Article numbereabl8070
Number of pages15
JournalScience Advances
Volume8
Issue number24
DOIs
Publication statusPublished - Jun 2022

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