Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality

Abstract

Background Environmental, lifestyle, and occupational exposures on semen quality have been investigated in epidemiological studies with inconsistent results. Genetic factors involved in toxicant activation and detoxification have been examined in relation to the risk of outcomes such as cancer, cardiovascular, and neurologic disorders. However, the effect of common genetic variants in the metabolism of toxicants on semen quality parameters has rarely been evaluated. In this analysis, we evaluated functional SNPs of three genes of the glutathione-S-transferase (GSTM1, GSTT1, GSTZ1) enzyme family. Methods Participants were 228 presumed fertile men recruited as part of a community-based study. Semen outcome data from this study included total sperm count and concentration, sperm morphology, and sperm DNA integrity and chromatin maturity. DNA was obtained from 162 men from a mouth-rinse sample and genotyped for the presence of GSTT1-1 and GSTM1-1 null genotypes and the GSTZ1 SNPs at positions 94 (rs3177427) and 124 (rs3177429). We used multivariable linear regression to assess the relationship between each genotype and sperm outcomes. Results Overall, our results did not reveal a consistent pattern between GSTM1 and GSTZ genotypes and increased occurrence of adverse sperm outcomes. However, the GSTT1 non-null genotype yielded the coefficients with the largest magnitude for sperm count and sperm concentration (β= −0.528, 95% CI −1.238-0.199 and β= −0.353, 95% CI −0.708-0.001, respectively), suggesting that it might be adverse. Conclusions These results indicate that common polymorphisms in GST genes do not negatively impact sperm parameters in healthy men with good semen quality. Contrary to expectations, the GSTT1 non-null genotype was associated with reduced sperm concentration and count in semen. Further study with a larger study size and inclusion of gene-exposure interactions is warranted.

The Association of Seminal Plasma Antioxidant Levels and Sperm Chromatin Status with Genetic Variants ofGSTM1andGSTP1(Ile105Val and Ala114Val) in Infertile Men with Oligoasthenoteratozoospermia

“…This finding had been previously confirmed in fertile men with good semen quality [17]. Olshan et al showed that gene polymorphisms of GSTM1, GSTT1, and GSTZ1 are not correlated with sperm quality.…”

Missense mutation in glutathione-S-transferase M1 gene is associated with sperm motility and ATP content in frozen-thawed semen of Holstein-Friesian bulls

“…Most findings confirmed its influence on sperm concentrations (Aydemir et al, 2007;Finotti et al, 2009;Olshan et al, 2010) but also on sperm motility and increased oxidative damage of sperm plasma membrane in idiopathic infertility patients with GSTM1 null genotype (Aydemir et al, 2007). GSTM1 null genotype has also been studied in relation to susceptibility to male infertility, particularly to idiopathic oligozoospermia (Wu et al, 2013) and oligoasthenoteratoa zoospermia (OAT) (Tang et al, 2012).…”

“…GST genes have been studied in relation to semen quality (Olshan et al, 2010) and genetic susceptibility of infertility with impaired spermatogenesis in men (Xu et al, 2013;Ying et al, 2013). Polymorphisms in GSTs genes, mostly null and non-null genotype, were associated with oligoazoospermia, azoospermia and idiopathic male infertility risk (Aydemir et al, 2007;Wu et al, 2008;Finotti et al, 2009;Roshdy et al, 2014) or DNA damage of sperm exposed to air pollution (Rubes et al, 2007).…”

The Enzymatic Antioxidant System of Human Spermatozoa

“…It is interesting to note that not all the GST isoforms may play a significant role in the protection of spermatozoa against oxidative stress; for example, the levels of GST A1-1 and P1-1 in seminal plasma are similar in fertile or infertile men [87]. Recently, it was reported that GSTM1, GSTT1, and GSTZ1 polymorphisms seem not to be associated with sperm quality in humans, but only GSTT1 was associated with reduced sperm concentration [88]. Based on all these studies, it is evident that GSTs are playing different roles depending on the isoform considered and more research is necessary to have a complete picture of the participation of this large family of antioxidant enzymes in male reproduction.…”