Evaluation of methylenetetrahydrofolate reductase and S-adenosyl-methionine level in male infertility: A case-control study

Baranizadeh K, Khadijeh Baranizadeh, Bahmanzadeh M, Maryam Bahmanzadeh, Tavilani H, Heidar Tavilani, Tayebeh Ghiasvand, Ghiasvand T, Amiri I, Iraj Amiri, Mahnaz Yavangi, Yavangi M, Gholamreza Shafiee
International journal of reproductive biomedicine · 2022 · vol. 20(4) , pp. 299–306 · doi:10.18502/ijrm.v20i4.10902 · PMID:35822186 · PMC9260066
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This study found lower MTHFR activity and SAM levels in men with oligozoospermia compared to normozoospermic men, correlating with reduced sperm concentration, morphology, and motility.

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This case-control study compared MTHFR enzyme activity and S-adenosylmethionine (SAM) levels in seminal plasma between normozoospermic and oligozoospermic men. The researchers found that both MTHFR activity and SAM concentrations were significantly lower in the oligozoospermia group, with a positive association observed between these two variables within each cohort. The authors suggest that reduced methylation capacity due to low MTHFR activity may impair spermatogenesis, although the study explicitly notes it excluded participants with identifiable causes of infertility such as varicocele or infection. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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Abstract

BACKGROUND: Methylenetetrahydrofolate reductase enzyme (MTHFR) plays a key role in regulating folate balance, converting homocysteine to methionine, and producing s-adenosylmethionine (SAM) that plays a role in the methylation process. OBJECTIVE: This study aimed to determine MTHFR activity and SAM level in men with normozoospermia and oligozoospermia. MATERIALS AND METHODS: 30 oligozoospermic and 30 normozoospermic men as controls were enrolled in this case-control study. Semen analysis was conducted according to the world health organization criteria. All semen samples were collected after 3-5 days of sexual abstinence. The sperms were evaluated by sperm test video software. All subjects SAM level was measured by enzyme-linked immunosorbent assay kit, and MTHFR were measured manually. RESULTS: 2 groups had a significant difference in sperm morphology (p = 0.02), concentration (p = 0.02) and motility (p = 0.03). The MTHFR activity in normozoospermic and oligozoospermic groups had significantly differences (p = 0.01). The level of SAM in the semen of oligozoospermic men was statistically lower than normozoospermic men (p = 0.03). Also, there was a positive association between MTHFR enzyme activity and SAM level in the normozoospermia group (p = 0.02, β = 0.67) and oligozoospermia group (p = 0.03, β = 0.54). CONCLUSION: MTHFR activity and SAM concentration were statistically lower in oligozoospermia men. It seems they can affect sperm concentration, morphology, and motility.
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In the present study, it was observed that the level of SAM in the normozoospermia group was higher than in the oligozoospermia group. It was also found that the rate of MTHFR activity in normozoospermia individuals was significantly higher than oligozoospermia group. MTHFR activity and its product, SAM, play a role in sperm evolution, morphology, and motility. It seems that the activity of the MTHFR enzyme is an enzyme involved in folic acid metabolism and may be an important factor in spermatogenesis.

Coi Statement

The authors declare no conflict of interest.

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