Disrupted expression of long non-coding RNAs in the human oocyte: the possible epigenetic culprits leading to recurrent oocyte maturation arrest.

PURPOSE

To depict the lncRNA expression during human oocyte maturation and explore the lncRNAs leading to recurrent oocyte maturation arrest.

METHODS

LncRNA sequencing was performed on pooled RNA from 20 oocytes of each group (recurrent oocyte maturation arrest (ROMA), of germinal vesicle (GV), metaphase I (MI), or metaphase II (MII) stages. Bioinformatics software was deployed to compare the lncRNA differential expression between the normal and ROMA oocytes. The co-expression of lncRNA/mRNA was illustrated with the Cytoscape software. The pooled RNA from every 10 oocytes of each group (ROMA, GV, MI, MII) was extracted for further qPCR validation.

RESULTS

There were 17 downregulated and 3 upregulated lncRNAs in the ROMA oocyte. Among them, co-expression analysis indicated that NEAT1 and NORAD were both downregulated. Basing on the KEGG enrichment analysis, PRCKA and JAK3 might be the target genes in the PI3K-Akt pathway and modulated by NEAT1 and NORAD. As validated by qPCR, the expressional levels of lncRNA candidates (NEAT1 and NORAD) and their target genes (PRKCA and JAK3) were confirmed to be extremely lower in the ROMA oocyte than in the normal oocyte.

CONCLUSION

By targeting the PI3K-Akt pathway genes PRKCA and JAK3, the abnormal expression of NEAT1 and NORAD is suggested to impede oocyte maturation and impair oocyte genome integrity.