AIRE Gene Expression in Oxidative Stress and Inflammatory Load in Female Infertility

Background & Objective: Female infertility, affecting over 2,700 per 100,000 women globally, is influenced by genetic, hormonal, immunological, and environmental factors. Autoimmune dysfunction, particularly involving the AIRE gene, which regulates immune tolerance, may impair ovarian and endocrine function. Additionally, oxidative stress (indicated by malondialdehyde, MDA) and chronic inflammation (marked by IL-6 and CRP) negatively affect oocyte quality, implantation, and hormonal balance. This study aimed to evaluate the combined role of AIRE gene expression, oxidative stress, and inflammation in female infertility. Materials & Methods: A case-control study was conducted on 300 women (18-45 years), including 150 infertile cases and 150 fertile controls from hospitals in Kerala. Blood samples were analyzed for biochemical, hormonal, and genetic parameters. IL-6, CRP, and MDA were measured using ELISA, while AIRE gene expression was assessed by RT-PCR. Statistical analysis was performed using Stata 17.0, with P<0.05 considered significant. Results: Infertile women showed significantly elevated CRP, IL-6, and MDA levels, indicating increased inflammation and oxidative stress. AIRE gene expression was significantly downregulated (P<0.01). ROC analysis identified CRP and MDA as strong predictors of infertility, whereas AIRE had limited diagnostic performance. Notably, AIRE expression showed a negative correlation with CRP, IL-6, and MDA. Conclusion: Female infertility is strongly associated with immune dysregulation, inflammation, and oxidative stress. Reduced AIRE expression, along with elevated inflammatory and oxidative markers, highlights its potential as a biomarker of immune imbalance. These findings support the development of immune-targeted diagnostic and therapeutic approaches in infertility management.