Integrated Role of NRF2 and p53 Gene Expression in Hormonal and Biochemical Dysregulation Among Infertile Males.

Abstract

Objective: Male infertility is a multifactorial condition often linked to oxidative stress and apoptosis. Key molecular regulators, such as NRF2 (antioxidant defense) and p53 (cell cycle and apoptosis), are influenced by hormonal and inflammatory pathways; however, their combined role in infertility remains underexplored. This study investigates the integrated expression of NRF2 and p53 genes and their association with hormonal, inflammatory, and biochemical markers in infertile males.

Methods: A case-control study was conducted on 300 males (150 infertile, 150 fertile controls). Gene expression (NRF2, p53) was analyzed using RT-PCR. Hormonal (FSH, testosterone, estradiol), inflammatory (IL-6), and biochemical (SOD, PSA) markers were measured via ELISA. Statistical analysis included t-tests, ROC, scatter plot, and multiple regression.

Results: Infertile men showed significantly reduced NRF2 expression and SOD levels, with elevated FSH, estradiol, IL-6, PSA, and p53 expression (p<0.001). ROC analysis identified FSH and NRF2 as strong predictors of infertility. Regression revealed IL-6 and PSA as significant positive predictors of p53 expression, while SOD positively correlated with NRF2. Scatterplots highlighted contrasting biomarker associations for NRF2 and p53.

Conclusions: Combined dysregulation of NRF2 and p53, driven by oxidative, hormonal, and inflammatory factors, plays a critical role in male infertility. These genes hold promise as both diagnostic biomarkers and therapeutic targets.