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. 2022 Jul;54(6):e14400.
doi: 10.1111/and.14400. Epub 2022 Mar 11.

Are UMFA (un-metabolized folic acid) and endocrine disruptor chemicals (EDCs) co-responsible for sperm degradation? An epigenetic/methylation perspective

Yves Menezo  1 , Patrice Clement  1 , Kay Elder  2
Affiliations

Are UMFA (un-metabolized folic acid) and endocrine disruptor chemicals (EDCs) co-responsible for sperm degradation? An epigenetic/methylation perspective

Yves Menezo et al. Andrologia. 2022 Jul.
No abstract available

Keywords: EDCs; UMFA; epigenetic/methylation resetting; folic acid; sperm.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Perturbation in germline methylation/epigenetic process in the male embryo: the impact of UMFA and oxidative stress. (1) Weak DHFR activity (Bailey & Ayling, 2009) blocks the entry of UMFA into the folate cycle and leads to a Michaelis and Menten effect, a vicious cycle that further inhibits DHFR activity. (2) MTHFR SNPs (Methylenetetrahydrofolate Reductase single nucleotide polymorphisms), especially T677T, reduce MTHFR activity and impair the formation of 5‐MTHF (5 methyl tetrahydrofolate). The cycle pathway between THF and 5‐MTHF can be completely blocked; the cycle can be reversed with an accumulation of UMFA. (3) UMFA and active natural folate 5‐MTHF compete for receptor and transporters (Smith et al. 2017) in order to enter cells, and this exacerbates the situation by decreasing the availability of the natural folate for homocysteine regeneration. (4) EDCs (endocrine disruptor chemicals) exacerbate a process of undue demethylation via oxidative stress (Menezo et al., 2015). DHFR, dihydrofolate reductase; FolR1, folate receptor 1; MS, methionine synthase; MTHFR, methylenetetrahydrofolate reductase; SAH, S‐adenosyl homocysteine; SAM, S‐adenosyl‐Methionine; SLC19A1 and A1, folates transporters; THF, tetrahydrofolate
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