Dynamic changes in the transcriptome of oocytes during adolescent-onset PCOS in mice

Abstract

AbstractAn adolescent-onset PCOS mouse model was established using dehydroepiandrosterone (DHEA) to explore temporal changes in the transcriptome of oocytes. Oocyte RNA sequencing was conducted using smart-seq technology. Genes with a similar expression trend over time were identified using trend analysis. Significant selected genes were those exhibiting an opposite trend in the DHEA group compared with the control group. KEGG pathway enrichment analysis and gene regulatory network diagrams were examined for signaling pathways to identify potential hub genes related to the pathogenesis of PCOS. Oocytes were collected at six consecutive time points during the modeling of PCOS in mice. Four main trends of gene expression were extracted, of which six combinations of Venn diagrams were generated. KEGG pathway analyses revealed that hub genes were mainly enriched in oxidative phosphorylation, cell cycle, P53 signaling pathway and related pathways. mtDNA coding subunits (mt-Nd1, 2, 3, and 6, mt-Co1 and 2), cytochrome oxidase (Cox8a, 7a2l, and 4i1), NADH-ubiquinone oxidoreductase (Ndufa1, 2 and 6, Ndufb 9), and Uqcrq were markedly up-regulated in the DHEA group. Cell cycle-related genes (Skp1, Ccnb1, Orc1 and 5, Wee2, Mapk3, Cdc20) were abnormally down-regulated in the DHEA group. These genes may be potential candidates that have temporal actions in the pathogenesis of PCOS. This study provides a novel insight into the altered transcriptome of oocytes from PCOS mice and potential key genes that may play important roles in the development of PCOS.