An Exploratory Study on Transcriptomic Profiling of Circulating miRNA Associated with Hub Genes in the Development of Polycystic Ovary Syndrome

Exosomal lncRNA-miRNA-mRNA regulatory axis may drive inflammation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in reproductive-aged women and is associated with reproductive dysfunction, metabolic abnormalities, and chronic low-grade inflammation. Emerging evidence highlights the role of circulating exosomal inflammatory cytokines and non-coding RNAs (ncRNAs) in PCOS pathogenesis. This case-control study aimed to investigate the expression of exosomal mRNA expression levels of IL-6 and TGF-β1, and selected long non-coding RNAs (MALAT1, NEAT1, H19, GAS5, and HOTAIR) in women with PCOS and to elucidate the associated lncRNA-miRNA-mRNA regulatory network. Exosomes were isolated from serum samples of PCOS and healthy subjects using a commercial exosome isolation kit. Exosomes were characterized by FESEM, DLS, zeta potential analysis, and flow cytometry, followed by RNA extraction and cDNA synthesis. Bioinformatic analyses were performed to construct regulatory networks, followed by molecular docking to evaluate the potential interactions between lncRNAs and miRNAs. A heatmap illustrating gene expression patterns was generated in R using the pheatmap package. Characterization of the isolated vesicles confirmed a spherical morphology, nanoscale dimensions, and the presence of exosomal surface markers. The exosomal mRNA expression levels of IL-6 and TGF-β1 were significantly upregulated in patients with PCOS. Among the lncRNAs analyzed, GAS5, NEAT1, and H19 were significantly increased, whereas MALAT1 and HOTAIR were markedly decreased. Network analysis identified miR-146a-5p and miR-29b-3p as key regulatory hubs associated with IL-6 and TGF-β1 mRNA expression. Molecular docking suggested a higher likelihood of stable binding, particularly for the H19/miR-146a-5p and NEAT1/miR-29b-3p complexes. These findings may suggest a potential role for dysregulation of the exosomal lncRNA-miRNA-mRNA regulatory axis, particularly involving IL-6 and TGF-β1 mRNA expression, in the inflammatory processes associated with PCOS. In addition, circulating exosomal ncRNAs and inflammation-related factors may represent potential non-invasive biomarkers and possible therapeutic targets for PCOS. However, these associations require further functional and validation studies.

A Review of microRNAs in the Post-transcriptional Regulation and its Clinical Manifestation in the Polycystic Ovary Syndrome

A lactylation-related transcriptional signature as candidate biomarkers for the early detection of polycystic ovary syndrome: an integrated genomic analysis

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder that negatively impacts women’s reproductive and metabolic health, leading to complications such as irregular menstruation, infertility, obesity, and metabolic syndrome. Current diagnostic methods, which primarily rely on clinical symptoms and hormone levels, lack specificity in early detection. This study aimed to identify lactylation-related transcriptional signatures as candidate biomarkers for the early detection of PCOS. We conducted a comprehensive bioinformatic analysis using transcriptomic data from granulosa cells of PCOS patients in the GEO database. Patients were categorized into two molecular subtypes via consensus clustering based on the expression of lactylation-related genes. Subsequently, diagnostic models were constructed and validated to evaluate the potential of these transcriptional signatures as early diagnostic markers. External validation was performed using an independent dataset, and selected candidate genes were further examined in DHEA-treated KGN cells. We identified nine key genes (HK3, SDC3, TGFBI, ZYX, LSP1, HMGA1, LCP1, B3GAT1, and ZNF280C) that were significantly differentially expressed in PCOS granulosa cell transcriptomic datasets. Pathway enrichment analyses revealed their involvement in energy metabolism, cell proliferation and apoptosis, which highlights their potential roles in PCOS pathogenesis. A random forest-based diagnostic model showed high internal predictive performance, with an ROC AUC of 0.993; however, external validation yielded a lower AUC of 0.628, indicating limited generalizability and the need for further validation. These findings suggest that lactylation-related transcriptional signatures may serve as potential candidate biomarkers for the early detection of PCOS. However, because this study was based primarily on transcriptomic inference and did not directly measure lactylation modifications, the results should be interpreted as hypothesis-generating. Future studies should validate these biomarkers in larger clinical cohorts, primary granulosa cells, and through direct lactylation or proteomic assays.

Metabolic profiling of human follicular fluid to unravel the pathways involved in polycystic ovary syndrome – a systematic review

FF metabolomics reveals a PCOS signature characterized by lipid, amino acid, and energy metabolism dysregulation, potentially contributing to follicular dysfunction, and should consider PCOS phenotypic heterogeneity.

Dysregulated Acetate Metabolism and Cholesterol Biosynthesis in Cumulus Cells of Women with Polycystic Ovary Syndrome.

Association of miR-21 Expression and hormonal disorder in woman with polycystic ovary syndrome

It is indicated that miR-21 could be a potential biomarker for assessing the disease course and metabolic disorders in PCOS and more large-scale studies are needed to validate its diagnostic and prognostic value.