The Study of MTHFR Methylation on Sperm Parameters in Infertile Males: A Case-Control Study

The important roles of aberrant DNA methylation on semen abnormality have been demonstrated. Alternatively, 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a vital enzyme to regulate the sperm DNA methylation patterns. This study aimed to investigate the methylation of MTHFR at differentially methylated regions (DMR) and the correlation between sperm DNA methylation patterns with semen quality parameters for assessing reproductive health and fertility status.

In this case-control study, semen samples were collected from 30 infertile (asthenospermia and oligoasthenoteratospermia), and 15 healthy men. Following the modification of DNAs by sodium bisulfite treatment, the methylation status of the MTHFR gene at MDRs was evaluated by the quantitative methylation specific PCR (qMSP) method.

Men with oligoasthenoteratospermia showed a statistically significant difference in mean MTHFR-DMR methylation levels compared to controls (P=0.047) and asthenospermia (P=0.034). Moreover, significant trends of decreasing values were observed in all parameters of the ejaculate (sperm concentration, their overall motility or vitality, and morphology) in men with asthenospermia and oligoasthenoteratospermia. These findings suggest a potential association between increased MTHFR-DMR methylation and reduced semen quality such as spermatozoa count (P=0.002), spermatozoa concentration (P=0.003), progressive (P=0.019), and normal morphology (P=0.003).

We found that abnormal DNA methylation of MTHFR at DMR region was correlated with decreased sperm parameters and therefore male infertility. Further research is needed to explore the mechanisms affecting of MTHFR methylation on male infertility.