Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve.

BACKGROUND

The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (mA) methylation regulate mRNA fate and translational efficiency. However, whether mA methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed mA transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group).

RESULTS

mA methylation distribution was highly conserved and enriched in the CDS and 3'UTR region. Besides, an increased number of mA methylated genes were identified in the older group. Bioinformatics analysis indicated that mA methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by mA. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by mA, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary.

CONCLUSIONS

Hence, our finding revealed the transcriptional significance of mA modifications and provide potential therapeutic targets to promote fertility reservation for aging women.