Single-cell transcriptome analysis of human oocyte ageing

Oocyte ageing is a key bottleneck and intractable challenge for in vitro fertilization treatment of aged female patients. The underlying molecular mechanisms of human oocyte ageing remain to be elucidated. Hence, this study aims to investigate the key genes and relevant biological signalling pathways involved in human oocyte ageing. We isolated mRNA for single-cell RNA sequencing from MII human oocytes donated by patients undergoing intracytoplasmic sperm injection. Nine RNA-seq datasets were analyzed, which included 6 older patients(average 42.67 +/- 2.25 years) and 3 younger patients (average 25.67 +/- 2.08 years). 481 differentially expressed genes (DEGs) were identified, including 322 upregulated genes enriched in transcription, ubiquitination, epigenetic regulation, and cellular processes, and 159 downregulated genes enriched in ubiquitination, cell cycle, signalling pathway, and DNA repair. The STRING database was used to analyse protein-protein interactions, and the Cytoscape software was used to identify hub genes. From these DEGs, 17 hub genes were identified including 12 upregulated genes (UBE2C, UBC, CDC34, UBR1, KIF11, ASF1B, PRC1, ESPL1, GTSE1, EXO1, UBA1, KIF4A) and 5 downregulated genes (UBA52, UBE2V2, SKP1, CCNB1, MAD2L1). The significant key biological processes that are associated with these hub genes include ubiquitin-mediated proteolysis, ubiquitination-related pathways, oocyte meiosis, and cell cycle. Among these, UBE2C may play a crucial role in human oocyte ageing.

Automated summary

This study investigated key genes and biological signalling pathways related to human oocyte ageing by analyzing RNA-seq data from MII human oocytes. The differentially expressed genes identified were enriched in transcription, ubiquitination, cell cycle, and other processes. Hub genes, such as UBE2C, may play crucial roles in the ageing of human oocytes.