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 (m(6)A) methylation regulate mRNA fate and translational efficiency. However, whether m(6)A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m(6)A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group). Results m(6)A methylation distribution was highly conserved and enriched in the CDS and 3'UTR region. Besides, an increased number of m(6)A methylated genes were identified in the older group. Bioinformatics analysis indicated that m(6)A 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 m(6)A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m(6)A, 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 m(6)A modifications and provide potential therapeutic targets to promote fertility reservation for aging women.