همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Elucidating Inflammatory Pathways in ‎‎Polycystic Ovary Syndrome: A ‎‎Transcriptomic Investigation of Granulosa ‎‎Cell Gene Expression

نویسندگان :

Mobina Afshari Kave¹ Farinaz Behfarjam² Maryam Shahhosseini³ Mostafa Rafiepour ‎⁴ Zahra Safaei Nezhad⁵

1- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran 2- Department of Genetics, Faculty of Science, University of Danesh Alborz, Tehran, Iran 3- Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 4- Department of Genetics, Faculty of Science, University of Danesh Alborz, Tehran, Iran 5- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran

کلمات کلیدی :

Polycystic Ovary Syndrome،Granulosa Cells‎،RNA-seq،Inflammatory response،Bioinformatics

چکیده :

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder affecting a significant proportion of women, ‎‎leading to diverse symptoms such as irregular menstrual cycles, hyperandrogenism, and ovarian cyst formation. While ‎‎the exact cause remains unclear, increasing evidence suggests a critical role of inflammation in the pathophysiology of ‎‎PCOS (Singh and Pal, 2023). Granulosa cells (GCs), which are essential for follicular development and hormone ‎‎production, are often dysregulated in PCOS, contributing to ovarian dysfunction (Dompe and Kulus, 2021). This study ‎‎aims to investigate the inflammatory mechanisms underlying PCOS, with a focus on gene expression changes in ‎‎granulosa cells, using a transcriptomic approach. To better understand the molecular underpinnings of this disorder, we ‎‎performed transcriptomic profiling of GCs from PCOS patients compared to healthy controls using RNA ‎‎sequencing(GSE138518). Differential gene expression analysis, conducted using DESeq2, revealed 68 genes with ‎‎significantly increased expression and 119 genes with decreased expression in PCOS GCs. Functional enrichment ‎‎analysis of these genes highlighted the involvement of inflammatory pathways, immune responses, and cell signaling. ‎‎Notably, pathway enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes ‎‎‎(KEGG) revealed that the upregulated genes were primarily linked to inflammation and immune system regulation, ‎‎suggesting that inflammation may be central to the pathophysiology of PCOS. In a more detailed examination, network ‎‎analysis identified several hub genes that are critical to inflammatory responses in PCOS. These include ITGB2, ‎PTPRC, ‎SPI1, FCGR3B, HCK, FCGR2A, ITGAX, CSF3R, S100A9, STAT1, and CSF2RB. These genes are involved ‎in immune ‎cell signaling, phagocytosis, leukocyte activation, and cytokine production. For example, ITGB2 and ‎ITGAX are integral ‎to immune cell adhesion and activation, while PTPRC (also known as CD45) regulates T-cell ‎receptor signaling. SPI1 ‎plays a key role in the differentiation of macrophages and dendritic cells, and HCK is involved ‎in immune cell signaling ‎and inflammation. Furthermore, S100A9 and CSF3R are crucial for neutrophil recruitment ‎and activation, amplifying ‎the inflammatory response. STAT1 and CSF2RB are critical transcription factors and ‎cytokine receptors that regulate ‎immune responses and hematopoiesis. The upregulation of these genes suggests a ‎persistent inflammatory environment in ‎the ovaries of PCOS patients, with implications for ovarian dysfunction and the ‎systemic metabolic abnormalities often ‎observed in PCOS. These findings support the hypothesis that chronic ‎inflammation plays a central role in the disease ‎process and highlights potential therapeutic targets. In conclusion, our ‎study provides valuable insights into the ‎inflammatory network in PCOS, identifying key hub genes that could serve as ‎biomarkers or targets for therapeutic ‎intervention. Future research should focus on further elucidating the role of these ‎genes in ovarian ‎pathophysiology and ‎exploring potential anti-inflammatory treatments to improve clinical outcomes for ‎‎PCOS patients. ‎