VPS34 regulates RAB7 activation and Retromer localization to autophagosomes and mitophagy in oocytes
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ABSTRACT: To investigate the role of Vps34 during oocyte development, we crossed female Vps34f/f mice with Gdf9-Cre and Zp3-Cre male transgenic mice for Cre recombinase specifically in oocytes at either primordial or early growing stages. Our results revealed that Vps34 plays a key role in oocyte cytoplasmic maturation. In order to reveal the changes in oocyte transcriptome level caused by Vps34 deletion, we conducted transcriptome sequencing on oocytes at GV stage, MII stage and 2cell embryo of ZcKO, and analyzed the changes in transcripts at these three stages. Transcriptome sequencing results showed that the oocytes and 2cell embryos of ZcKO were enriched with a large number of transcription and transport-related differential genes, and the 2cell stage had the most differential genes, which was the key period for the occurrence of major ZGA. Further analysis of transcription-related genes revealed that the enriched major ZGA genes were all down-regulated in 2cell of ZcKO mice. In addition, differential genes involved in autophagy were enriched in ZcKO 2cell, with HPG abnormally increased. Autophagy is the main degradation pathways of maternal proteins in early embryonic development, and degradation of maternal proteins is necessary for the normal process of ZGA, which occurs prior to major ZGA and even during oocyte maturation, when defects appear to be irremediable later. These results suggest that Vps34 deletion leads to degradation inhibition of maternal factors and impaired major ZGA, leading to embryonic development arrest.
ORGANISM(S): Mus musculus
PROVIDER: GSE216465 | GEO | 2023/09/01
REPOSITORIES: GEO
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