This case-control study examined global m⁶A RNA methylation levels, expression of m⁶A writer/reader/eraser (WRE) genes, and selected microRNAs in granulosa cells (GCs) from 23 women with PCOS (labeled 'PMOS' in this paper) vs. 23 age- and BMI-matched controls undergoing IVF.
Global m⁶A was significantly elevated in PCOS GCs; writer (METTL3, METTL14, WTAP, RBM15, VIRMA) and reader (YTHDF1, YTHDF3, YTHDC1) transcripts were upregulated, while eraser transcripts (FTO, ALKBH5) were downregulated. Elevated m⁶A, METTL3, METTL14, and YTHDF1 positively correlated with androgen excess, AMH, and reduced oocyte fertilization rates. miR-20b was downregulated and miR-607 was upregulated.
- The study is observational and cannot establish causality between epitranscriptomic changes and PCOS pathophysiology. - mRNA-level expression of WRE genes was assessed by RT-qPCR without protein-level validation. - Small sample size (n=23 per group) limits generalizability.
Widespread epitranscriptomic dysregulation—particularly elevated m⁶A and imbalanced writer/eraser expression—in granulosa cells may contribute to impaired folliculogenesis and reduced fertilization in PCOS, but findings are currently foundational and not yet actionable clinically.
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