Association between the MTHFR-C677T isoform and structure of sperm DNA

The aim of this study is to evaluate whether the MTHFR contribution to male decreased fertility can be attributable to anomalies in sperm nucleus DNA structure in relation to defective methylation.

The presence of MTHFR C677T, contributing at most for male infertility, was determined from a venous blood sample, using real-time polymerase chain reaction (PCR). Sperm DNA fragmentation (SDF) and sperm nucleus decondensation index (SDI) measurements were performed using acridine orange and flow cytometry. SDF and SDI of men MTHFR C677T heterozygous or homozygous were compared to a general population of hypo-fertile patients RESULTS: SDF is not increased either in homozygous or heterozygous carriers of MTHFR C677T. In contrast, SDI is increased with a higher incidence in homozygous (p = 0.0006) than in heterozygous (p = 0.029) patients when compared with the control population. Using a critical threshold of 20% for either SDI or SDF assayed with our technique, the percentage of patients with results higher than this value is not significant with respect to fragmentation (0.128), but is significantly increased for decondensation (0.0003).

Defective methylation linked to MTHFR may contribute to sperm pathogenesis via increased SDI. After DNA structure analysis, especially SDI, treatment with 5-methyl tetrahydrofolate (MTHF), the metabolite downstream from the action of MTHFR, should be recommended as a therapeutic approach. Patients with a high SDI should be tested for MTHFR isoforms as part of a healthcare policy.