Exploration potential regulatory mechanisms in ovarian injury of mice exposed to low-pressure hypoxia through whole transcriptome sequencing analysis [RNA-seq]

Chronic high-altitude hypoxia causes significant ovarian tissue damage. This study investigates the underlying mechanisms of ovarian injury in mice exposed to hypoxia, aiming to guide targeted therapy development. Mice were divided into either normal pressure (MP, n=15) or hypobaric hypoxia (PU, n=15) and samples from both groups were analyzed using whole-transcriptome sequencing data. Hub genes were identified through differential expression analysis and protein-protein interaction (PPI) network construction before their expression patterns were examined. Subsequently, functional enrichment was conducted. Key miRNAs, lncRNAs, circRNAs, and transcription factors (TFs) were ascertained. Finally, RT-qPCR and Western blotting (WB) were performed. Hmgcr, Ptgs2, and Mmp3 were identified as hub genes, all showing pronounced lower expression in PU samples. RT-qPCR analysis confirmed the downregulation of these genes, with WB analysis further demonstrating a significant reduction in their protein levels in PU samples. These hub genes were predominantly enriched in "oxidative phosphorylation" pathway. Furthermore, lncRNA-miRNA-mRNA, circRNA-miRNA-mRNA, and TF-mRNA regulatory networks were constructed. These networks highlighted key regulatory molecules, including the miRNA mmu-miR-144-3p, 2 lncRNAs (Miat and Neat1), 8 circRNAs (eg. novel_circ_041272-mu-miR-144-3p-Ptgs2), and 1 TF (Etv4). These results provide key insights for targeted ovarian injury therapies under low-pressure hypoxia.