Evaluation of Glutathione S-transferase Mu 3 (GSTM3) levels in sperm as a simple method to predict oxidative DNA damage and seminogram alterations

Abstract

Background. Previous evidence suggested sperm Glutathione S-transferase Mu 3 (GSTM3) to be essential for an appropriate mitochondrial function, plasma membrane stability and oxidative regulation of mammalian sperm. In humans, however, neither has this enzyme been related to semen alterations nor has it been reported to be associated to oxidative DNA damage and (in)fertility. Methods. The aim of the present study was to assess the utility of GSTM3 to predict spermiogram alterations and oxidative DNA damage in sperm. A total of 34 semen samples were collected, evaluated by conventional semen analysis, and subsequently cryopreserved. Frozen-thawed sperm samples were assessed for DNA fragmentation and the presence, localization and content of GSTM3. Results. Sperm GSTM3 content was positively associated to sperm quality parameters (P < 0.05). Specifically, lower levels of this antioxidant enzyme were observed in asthenoteratozoospermic and oligoasthenoteratozoospermic men (P < 0.05), but not idiopathic infertile patients (P > 0.05), when compared to normospermic samples. Moreover, sperm GSTM3 was negatively associated to oxidative DNA damage (P < 0.05). Finally, the ability to predict spermiogram alterations was determined by ROC curve analysis using GSTM3 alone (AUC of 0.89; P < 0.05), and in combination with oxidative DNA damage (AUC of 0.91; P < 0.05). Conclusions. Although the limited sample size of the present study warrants further studies and clinical trials with larger sample sets, our results set the ground for using GSTM3 as a novel biomarker and therapy target for male infertility and oxidative DNA damage in sperm.