Abstract
PURPOSE: By exploring the role of miRNAs in human oocyte development, the study was conducted to investigate the epigenetic mechanism contributing to the arrest of oocyte development. METHODS: In total, 140 oocytes from 22 patients were collected in the developmentally arrested oocyte (DAO) group, whereas 420 oocytes from 164 patients were harvested in the control group. The pooled RNA was extracted from all 20 oocytes to establish a RNA library. The total RNA of every ten oocytes was extracted for qPCR validation of miRNA candidates. Bioinformatic software was applied to explore the miRNA candidates and their target genes. RESULTS: Generally, the expression levels of miRNAs altered slightly during normal oocyte development but changed dramatically in the DAOs. Among the top 10 differential miRNAs, let-7a-5p and let-7g-5p, which were abundantly expressed throughout the oocyte development stages, had the broadest biological impact on oogenesis. Validated by qRT-PCR, both miRNAs were profoundly suppressed in the DAOs. During normal oocyte development, the expression levels of let-7a-5p and let-7g-5p at the GV stage were significantly higher than at MI and MII stages. Bioinformatic analysis demonstrated that let-7a-5p and let-7g-5p might regulate oocyte development by targeting PI3K-Akt, P53, cell cycle, and FoxO signaling pathways. CONCLUSIONS: There are dramatic differences in miRNA landscapes between the human oocytes with or without development arrest. In addition, the suppression of let-7a-5p and let-7g-5p might be associated with the occurrence of development arrest. The findings could provide therapeutic targets to correct the arrest of oocyte development in the future.