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. Granulosa cells (GCs), which are essential for follicular development and hormone production, are often dysregulated in PCOS, contributing to ovarian dysfunction. 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 (GSE۱۳۸۵۱۸). Differential
gene expression analysis, conducted using DESeq۲, revealed ۶۸ genes with significantly increased expression and ۱۱۹ 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 ITGB۲, PTPRC, SPI۱, FCGR۳B, HCK, FCGR۲A, ITGAX, CSF۳R, S۱۰۰A۹, STAT۱, and CSF۲RB. These genes are involved in immune cell signaling, phagocytosis, leukocyte activation, and cytokine production. For example, ITGB۲ and ITGAX are integral to immune cell adhesion and activation, while PTPRC (also known as CD۴۵) regulates T-cell receptor signaling. SPI۱ plays a key role in the differentiation of macrophages and dendritic cells, and HCK is involved in immune cell signaling and inflammation. Furthermore, S۱۰۰A۹ and CSF۳R are crucial for neutrophil recruitment and activation, amplifying the inflammatory response. STAT۱ and CSF۲RB 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
