Expression of IL-13 and HIF-2α Genes and Their Correlation with Serum VEGF Levels in Women with Primary Infertility

Background: Infertility is a multifactorial disorder influenced by hypoxia signalling, immune modulation, and angiogenesis, which collectively determine endometrial receptivity and implantation success. Key mediators, including Hypoxia-Inducible Factor-2α (HIF-2α), Interleukin-13 (IL-13), and Vascular Endothelial Growth Factor-A (VEGF-A), play essential roles in oxygen sensing, immune tolerance, and angiogenesis, respectively. However, their coordinated expression and diagnostic potential in infertility, particularly among Middle Eastern women, remain insufficiently understood. Objective: This study aimed to estimate the expression levels of HIF-2α and IL-13 genes and serum VEGF-A, and to assess their correlations and diagnostic performance in infertile women compared with fertile controls. Materials and Methods: A case-control study was conducted involving infertile patients and age-matched fertile women. Gene expression was analysed using real-time quantitative PCR (RT-qPCR) with melt curve validation, and serum VEGF-A concentrations were determined by ELISA. Results: Findings revealed significant downregulation of HIF-2α in infertile women (fold change = 0.189, p = 0.038), while IL-13 expression showed a non-significant decrease (fold change = 0.69, p = 0.458). Serum VEGF-A levels were significantly lower in infertile women than in controls (310 ± 60 vs. 480 ± 44 pg/ml, p≤0.005). ROC analysis indicated high sensitivity but poor specificity for all three markers. A positive correlation was observed between HIF-2α and IL-13, whereas VEGF-A showed no significant correlation with either gene. Conclusions: Infertility reflects disrupted molecular interactions among hypoxia sensing, immune regulation, and angiogenic pathways. Although single markers such as HIF-2α, IL-13, and VEGF-A show limited diagnostic accuracy, integrating them into multi-marker panels could enhance predictive value and guide the development of targeted therapies to improve endometrial receptivity and implantation outcomes.