Aswathy Sundaresh, Jiju J S, Arun William, Aswathi Rajan, Soumya Jose, Aswathy G, Aksa Simon, Vineetha Vijayan, Bobby Joseph, Ajitha E V, Sreeshma P Pillai, Dinesh Roy D
JBRA Assist. Reprod. 2026; 30 (2):294-301
Received August 14, 2025
Accepted June 05, 2026
Abstract
Background: 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.
Objective: 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.
Conclusion: 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.
