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

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

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.

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Author information

Authors and Affiliations

  1. Clinique de La Muette, 75016, Paris, France

    Dominique Cornet & Laetitia Fournols

  2. Clinique Natecia, 69008, Lyon, France

    Marc Cohen

  3. Laboratoire Clement, Avenue d’Eylau, 75016, Paris, France

    Arthur Clement, Patrice Clement & Yves Ménézo

  4. American Hospital, 92200, Neuilly sur Seine, France

    Edouard Amar & Yves Ménézo

  5. Centre Hospitalo Univesitaire d’Angers, 49000, Angers, France

    Paul Neveux & Yves Ménézo

  6. London Fertility Associates, Harley St, London, UK

    Yves Ménézo

Authors
  1. Dominique Cornet
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  2. Marc Cohen
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  3. Arthur Clement
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  4. Edouard Amar
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  5. Laetitia Fournols
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  6. Patrice Clement
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  7. Paul Neveux
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  8. Yves Ménézo
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Contributions

Dominique Cornet, MD, Gynecologist; Marc Cohen MD, Gynecologist; Laetitia Fournols, MD, Endocrinologist and Edouard Amar, Urologist; have been in charge of the clinical follow-up of the patients.

Arthur Clement, MD; Patrice Clement Dr. Pharm and Yves Menezo PhD, Dr. Sci; have been in charge of the biological technical aspect of the experiments (MTHFR, SDF and SDI determination).

Paul Neveux, MD, has been in charge of all the statistical follow-up and calculation.

Yves Menezo has designed the experiment and written the paper.

Corresponding author

Correspondence to Yves Ménézo.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Cornet, D., Cohen, M., Clement, A. et al. Association between the MTHFR-C677T isoform and structure of sperm DNA. J Assist Reprod Genet 34, 1283–1288 (2017). https://doi.org/10.1007/s10815-017-1015-2

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  • DOI: https://doi.org/10.1007/s10815-017-1015-2

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