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Published on: August 4, 2019
Integrated Role of NRF2 and p53 Gene Expression in Hormonal and Biochemical Dysregulation Among Infertile Males
Aswathy Sundaresh1, J S Jiju2, Arun William3
1Associate Professor, Medical Biochemistry, Sree Gokulam Medical College & Research Foundation, Venjaramoodu, Thiruvananthapuram, Kerala, India.
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.
Insights
Male infertility involves oxidative stress and apoptosis, linked to NRF2 and p53 gene dysregulation. This study highlights their combined role and potential as biomarkers for male infertility diagnosis and treatment.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Genetics
Background:
- Male infertility is multifactorial, with oxidative stress and apoptosis implicated.
- NRF2 (antioxidant defense) and p53 (cell cycle/apoptosis) are key regulators.
- Their combined role in male infertility is not well understood.
Purpose of the Study:
- To investigate the integrated expression of NRF2 and p53 genes in infertile males.
- To assess the association of NRF2 and p53 with hormonal, inflammatory, and biochemical markers.
- To explore their potential as diagnostic biomarkers for male infertility.
Main Methods:
- Case-control study with 150 infertile males and 150 fertile controls.
- Gene expression analysis (NRF2, p53) via RT-PCR.
- Measurement of hormonal (FSH, testosterone, estradiol), inflammatory (IL-6), and biochemical (SOD, PSA) markers using ELISA.
Main Results:
- Infertile men exhibited reduced NRF2 and SOD, with increased FSH, estradiol, IL-6, PSA, and p53 expression (p<0.001).
- FSH and NRF2 were identified as strong infertility predictors.
- IL-6 and PSA positively predicted p53 expression; SOD correlated with NRF2.
Conclusions:
- Dysregulation of NRF2 and p53, influenced by oxidative, hormonal, and inflammatory factors, is critical in male infertility.
- NRF2 and p53 show promise as diagnostic biomarkers.
- These genes represent potential therapeutic targets for male infertility.
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