Combined Effect of GSTT1 and GSTM1 Polymorphisms on Human Male Infertility in North Indian Population

Abstract

Genes of different pathways regulate spermatogenesis, and complexity of spermatogenic process indicates that polymorphisms or mutations in these genes could cause male infertility. Detoxification pathway is involved in the regulation of spermatogenesis by reducing oxidative stress and contributes to the maintenance of global methylation in concert with other pathways. Glutathione S-transferases (GSTs) belong to the family of phase II antioxidant enzymes involved in the cellular detoxification of various physiological substances. Glutathione S-transferases act as an antioxidant and protect spermatozoa from oxidative stress. Increase in the levels of reactive oxygen species (ROS) along with reduced activity of GSTs may result in sperm membrane damage and DNA fragmentation. A case-control study was done to elucidate the role of deletion polymorphism of GSTT1 and GSTM1 genes from GSTs family on idiopathic human male infertility. The study comprises 2 groups: 113 nonobstructive azoospermia patients and 91 healthy fertile controls. Genomic DNA was analyzed by polymerase chain reaction for GSTT1 and GSTM1 genes. The study showed statistically significant protective association of GSTT1 null genotype with human male infertility (odds ratio [OR]: 0.3, 95% confidence interval [CI] 0.143-0.9966, P = .048) but not with GSTM1 null genotype (OR: 0.66, 95% CI 0.3653-1.2234, P = .19). Also, combination of null genotypes of GSTM1 and GSTT1 confers protective effect (OR: 0.28, CI 0.0801-0.948; P = .04). Probably, individuals bearing GSTM1 and GSTT1 (-/-) genotypes may have protective effect by gene-gene interaction mechanism. In summary, our study underscores the significance of combined effect of GSTT1 and GSTM1 null genotypes in modulating the risk of male infertility.

Nutritional modifications in male infertility: a systematic review covering 2 decades

“…70 Results from animal studies indicate that insulin has the potential to rescue spermatogenesis in type 1 diabetic mice 74 as well as increase sperm motility and sperm concentration in rats. 9 Furthermore, it has been demonstrated that IGF-1 protects equine Leydig cells from undergoing apoptosis in vitro. 75 Spermatogenesis is an active cell division process that requires insulin and IGF-1.…”

“…1,2 Several different disorders can cause male infertility, including idiopathic oligospermia (low sperm counts, for which a specific treatment remains unknown), [3][4][5][6] complete asthenozoospermia (absence of sperm motility; implicated in 19% of infertile cases), 7 and isolated asthenozoospermia (low sperm motility, caused by sperm dysfunction, varicocele, infection, or genetic factors; implicated in 24% of infertile cases). [8][9][10] In the 1970s, several purported causes of male factor infertility received considerable attention. As a consequence, the World Health Organization published both new standardized diagnostic approaches toward male factor infertility 11 and standardized techniques of semen analysis.…”

Human Spermatozoa Quantitative Proteomic Signature Classifies Normo- and Asthenozoospermia

“…4. DISCUSSION Twenty-four percent of infertile men present with isolated AZS (14) caused by various factors including varicocele, infection or genetic causes (15)(16)(17). Many cases are however idiopathic in nature and no specific causes can be ascribed to the condition (18).…”

Association of the Glutathione S-transferases M1 and T1 polymorphism with male infertility: a meta-analysis

“…The characteristics of selected studies are summarized in Table 1. A total of 12 eligible studies met the inclusion criteria, including 11 studies for GSTM1 [14,15,[25][26][27][28][29][30][31][32][33] and 9 ones for GSTT1 [17,26,27,[29][30][31][32][33]. All the included studies were case-control studies.…”