Variations in Antioxidant Genes and Male Infertility.

Bolan Yu,Zhaofeng Huang

doi:10.1155/2015/513196

Abstract

Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.

Highlights

Reactive oxygen species (ROS), which are strongly linked with oxidative stress, are oxygen-derived free radicals that include superoxide anions, hydroxyl, peroxyl, alkoxyl radicals, and hydrogen peroxide [1]
A recent analysis encompassing 6934 subjects indicated that the GSTM1-null genotype was significantly associated with idiopathic oligozoospermia, while the null genotype of GSTT1 was significantly associated with normozoospermia and azoospermia, and the association between GSTM1 polymorphism and male infertility was observed in cohorts of both Asian and Caucasian groups [84]
The antioxidant enzyme system, which is largely regulated by the nuclear factor erythroid 2-related factor 2 (NRF2)-ARE system, may be one of the key components that play a protective role against ROS damage during spermatogenesis and for sperm function (Figure 1)

Summary

Introduction

Reactive oxygen species (ROS), which are strongly linked with oxidative stress, are oxygen-derived free radicals that include superoxide anions, hydroxyl, peroxyl, alkoxyl radicals, and hydrogen peroxide [1]. Antioxidant enzymes and molecules such as superoxide dismutases (SODs), glutathione (GSH), and catalases (CATs) are largely abundant in semen plasma or in sperm cells [8,9,10] Most of these genes, including NRF2, SOD, CAT, glutathione S-transferase (GST), glutathione peroxidase (GPX), and nitric oxide synthase (NOS), harbor sequence variants in humans, which in turn may cause male infertility in different ways. This review discusses the recent progress in the study of genetic variations in antioxidant genes that have associated with male infertility The findings of these studies indicate that functional polymorphisms in the NRF2, SOD, GST, NOS, CAT, and GPX genes may potentially contribute to genetic causes of male infertility. As the incidence of male infertility continues to increase, the analysis of its association with sequence variants in antioxidant gene may help understand the roles of antioxidant signaling network in ROS-related male infertility and facilitate validating its potential as genetic markers for the diagnosis and risk assessment for male infertility in the clinic

Antioxidant Enzymes in Spermatogenesis

Genetic Variations in Antioxidant Genes Associated with Male Infertility

GWAS Study in Male Infertility

Findings

Conclusions