P-094 Genetic variations of antioxidant genes may coordinate with lifestyle to define male fertility: A cross-sectional study with control group
Authors: Bach H  A , Bach T  T C , Tran D  P , Nguyen D  T 
Published: July 2024

Abstract

Study question
Are polymorphisms of the oxidative stress-related genes different between infertile men and reproductively healthy men? Does lifestyle contribute to fertility outcomes?

Summary answer
A strong association between the polymorphisms of two antioxidant genes and sperm quality was identified. The infertile men had higher BMI and alcohol usage.

What is known already
Antioxidant genes including catalase (CAT), superoxide dismutase (SOD), and nitric oxide synthase (NOS) play a critical role in spermatogenesis and sperm functions, especially in stress-response cell signaling pathways. Polymorphisms of antioxidant genes have been reported to be associated with gene function, hence sperm quality, ultimately affecting male fertility in various cohorts. Body mass index (BMI) is universally considered a marker of health reflecting whole health, nutrition, and lifestyle. Smoking and alcohol consumption expose the body to harmful chemicals and oxidative stress. Here, we examined the polymorphisms of antioxidant genes in Vietnamese men and the link with lifestyle to regulate fertility.

Study design, size, duration
This cross-sectional study with control group recruited from Hanoi Medical University Hospital from 2018-2020. The participants were divided into two groups regarding semen analysis based on WHO 2010 criteria. The participants gave consent, then were clinically examined, interviewed for lifestyle, and genetically analyzed for antioxidant gene variations. An extra inclusion criterion for the control men was having at least one healthy baby. The exclusion criteria were chromosome aberrations and Y chromosome microdeletion.

Participants/materials, setting, methods
The control group (N = 85) and infertile group (N = 107) were recruited. Semen analysis was carried out by the CASA instrument based on WHO 2010 criteria. Lifestyle characteristics including exercise (per week), smoking (yes/no), alcohol consumption (the threshold for “yes” was five standard drinks/occasion, at least one occasion/month) were recorded. Four variants SOD1:7958G&gt;A, SOD2:c.47T&gt;C, CAT:-262C&gt;T, and NOS3:-786C&gt;T were analyzed by Sanger sequencing. Pearson’s, Chi-squared (χ2), Wilcoxon rank-sum, ANOVA test, and Bonferroni correction were applied where specifically required.

Main results and the role of chance
The average age of the two groups was not different (31.96 ± 4.87 vs 31.93 ± 6.3 years old, p = 0.92). The body mass index (BMI) of infertile men was significantly higher than the control (24.84 ± 2.31 vs 23.53 ± 2.55 kg/m2, p = 0.00026). No significant difference was identified regarding exercise and smoking. Notably, 96.26% of infertile men consumed alcohol in comparison with 88.23% of the control (p = 0,034).
Genetically, SOD1:7958GA genotype and NOS3:-786CT genotype in the infertility group were significantly higher than in the control, OR = 2.191 (95% CI: 1.226–3.915, p = 0.004) and OR = 3.135 (95% CI: 1.591–6.180, p &lt; 0.001), respectively. The frequency of the SOD2:c.47TC genotype was significantly higher in the male infertility group than in the control (OR = 1.941, 95% CI: 1.063–3.595, p = 0.029). Individuals carrying the SOD1:GA+AA, SOD2:TC+CC, and CAT:CT/TT genotype pattern had an increased risk of male infertility (OR = 7.614, p = 0.007), suggesting that gene-gene interaction plays an important role in male reproduction. To our knowledge, this is the first report worldwide on the association between the SOD1:7958G&gt;A polymorphism and male infertility.
Together, the data suggest that antioxidant gene polymorphisms and lifestyle, especially alcohol usage, coordinate to regulate male fertility.

Limitations, reasons for caution
Direct measurement of oxidative stress in the semen of men having different gene variations would be required to ascertain the link between the polymorphisms of antioxidant genes and fertility. The sample size was relatively small, a larger sample size would be required to accurately represent the Vietnamese population.

Wider implications of the findings
The findings can assist in infertility diagnosis focusing on the group of higher infertile risk genetic variations. Interventions such as antioxidant supplements would be developed and applied, lifestyle advice would be given specifically for a group having high-risk gene variations to accurately target fertility issues.

Trial registration number
Not applicable