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. 2017 Oct;34(10):1283-1288.
doi: 10.1007/s10815-017-1015-2. Epub 2017 Aug 25.

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

Dominique Cornet  1 , Marc Cohen  2 , Arthur Clement  3 , Edouard Amar  4 , Laetitia Fournols  1 , Patrice Clement  3 , Paul Neveux  5 , Yves Ménézo  6   7   8   9
Affiliations

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

Dominique Cornet et al. J Assist Reprod Genet. 2017 Oct.

Abstract

Purpose: 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.

Methods: 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).

Conclusions: 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.

Keywords: DNA fragmentation; MTHFR isoform C677T; Nucleus decondensation; Sperm.

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Conflict of interest statement

Funding information

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Folic acid and the one carbon cycle (1-CC). MS methionine synthase, CBS cystathionine beta-synthase pathway, MTHFR methylenetetrahydrofolate reductase, THF tetrahydrofolate, SAM S-Adenosyl methionine, SAH S-Adenosyl homocysteine. The two steps transforming folic acid in THF are supported by the dihydrofolate reductase (DHFR)
Fig. 2
Fig. 2
Sperm DNA fragmentation (SDF) and sperm nucleus decondensation index (SDI) according to the MTHFR C677T status. And percent of the patients having a > 20% value. C control, HTZ heterozygotes, HMZ homozygotes
See this image and copyright information in PMC

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