مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
RNA-Seq Profiling of Granulosa Cells in Polycystic Ovary Syndrome: Insights into Immune Response Pathways
RNA-Seq Profiling of Granulosa Cells in Polycystic Ovary Syndrome: Insights into Immune Response Pathways
Mobina Afshari Kave,1Farinaz Behfarjam,2,*Maryam Shahhoseini,3Mostafa Rafie Pour,4Zahra Safaei Nejad,5
1. Department of Genetics, Faculty of Science, Science and Culture University 2. Department of Genetics, Faculty of Science, Danesh Alborz University 3. Royan Institute of Reproductive Biomedicine 4. Department of Genetics, Faculty of Science, Danesh Alborz University 5. Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Introduction: Polycystic ovarian syndrome (PCOS) affects 11-13% of women worldwide and remains a vastly understudied condition. It is characterized by insulin resistance, hyperandrogenism, irregular menstrual cycles, anovulatory infertility, and metabolic disorders. Understanding the contributing factors to PCOS is essential for developing personalized treatment strategies. Moreover, investigating new biomarkers, improving diagnostic criteria, and advancing treatment options are critical to enhancing the efficacy and precision of interventions, benefiting patients' overall quality of life. This article focuses on elucidating the molecular mechanisms underlying PCOS by analyzing RNA sequencing data from granulosa cell samples of both PCOS patients and healthy individuals.
Methods: The RNA-Seq dataset (GSE138518), comprising three samples from PCOS patients and three from healthy individuals' granulosa cells, was analyzed. Differentially expressed genes (DEGs) were identified using the DESeq package in R. Gene ontology and KEGG pathway enrichment analyses were performed with the clusterProfiler package. Finally, network visualization was carried out using STRING and Cytoscape software, and hub genes were identified based on their network degree.
Results: A total of 68 genes were identified as differentially expressed based on the thresholds of 2 < log2FC < -2 and Padj-value < 0.05, including 25 upregulated genes and 43 downregulated genes. The downregulated genes were found to be more significant than the upregulated ones. Notably, the downregulated genes were enriched in pathways related to phagocytosis and immune response, across all levels of Gene Ontology enrichment (biological process, cellular component, and molecular function). Additionally, most differentially expressed genes (DEGs) were enriched in the KEGG pathways associated with neutrophil extracellular trap formation and phagosome/immune response signaling. Key downregulated hub genes identified include PTPRC, TLR2, FCGR3B, MNDA, FCGR2A, HCK, SELL, LCP2, CD163, and FPR1.
Conclusion: PCOS patients suffer from chronic low-grade inflammation, potentially triggering mechanisms that increase ovarian androgen levels and disrupt ovulation. The identified hub genes are closely associated with immune response signaling pathways, indicating that decreased expression of these genes may contribute to the development of PCOS.