Transcriptomic Profiling Reveals Ageing-Related Molecular Signatures in Women with Diminished Ovarian Reserve

The increasing incidence of diminished ovarian reserve (DOR) among women undergoing assisted reproductive technology (ART) poses significant challenges, as DOR is associated with lower pregnancy and live birth rates. This study aimed to investigate the molecular signatures related to ageing in women with DOR and their potential implications for understanding the underlying mechanisms of DOR. We collected peripheral blood samples from 20 infertile women under 40 years of age, including 10 patients with DOR and 10 with normal ovarian reserve (NOR). Using DESeq2, we identified differentially expressed genes (DEGs) between the DOR and NOR groups. DOR-related ageing genes were obtained by intersecting DEGs with three senescence-related databases (CellAge, CSGene, SenMayo). Transcriptomic profiling identified 14 ageing-related DEGs, of which E2F2, SYT1, BNIP3L, AREG, FOXO3, CTNNAL1, RBM38, BCL2L1, ALOX15B, MITF, TOP1, TRIM10, and PCGF2 were upregulated, and PROX1 was downregulated, in the DOR group. Functional enrichment analysis indicated a strong association between these DEGs and processes related to oxidative stress, apoptosis, and mitochondrial dysfunction. The findings underscore the systemic molecular ageing abnormalities present in women with DOR, providing insights into potential targets for therapeutic intervention aimed at improving ART outcomes. Overall design: RNA-seq profiling of peripheral blood samples from infertile women under 40 years of age, including 10 patients with diminished ovarian reserve (DOR) and 10 with normal ovarian reserve (NOR)