Male otherwise it will be trapped in the methylenetetrahydrofolate

Male infertility is a global problem facing the married couples, for each one to five married couples the male partner is the one who responsible for the infertility (1). It is determined that one for each twenty males are suffering from oligospermia and around one to hundred males complaining from Azospermia (2).Infertility and sterility among males is a huge problem facing the couples, it could be influenced by several many factors that varies from genetic to environmental factors. (7) Infertility prevalence is increasing worldwide  .(8)

Nowadays there is upcoming great attention to discover hidden factors which may influence the male fertility status, one of those factors is the genetic background which may play a crucial role in unknown idiopathic male infertility (3).   

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Spermatogenesis process is controlled by several factors and governed by autosomal and Y-sex chromosomal gene expression incidents which are influenced by DNA methylation. Any defect in the gene expression may lead improper gene expression and may lead to infertility in males (9). 

 

·         Folic acid metabolism :

Folic acid, also known as pteroyl-glutamate or pteroylglutamic acid, is made up of pteroic acid and  l-glutamic acid (one or more strands).The functional form of folate is tetrahydrofolic acid (10).   

Methylene tetrahydrofolate-homocysteine methyltransferase, is an enzyme needed to convert the homocysteine to methionine using the methylenetetrahydrofolate to be converted to tetrahydrofolate. This is the process to maintain the folic acid in free active form otherwise it will be trapped in the methylenetetrahydrofolate form which is called folate trap.  Methyltetrahydrofolate trapping, or the “folate trap” will hinder the methionine biosynthesis and homocysteine methylation. Moreover, presence of folic acid in the methylene tetrahydrofolate form will avoid the folic acid to be polyglutamised and prevent it from the cell binding. Led the compound useless.(11)  

·         Folic acid metabolism disorders and gene polymorphism :

One of the most important enzyme needed for folic acid metabolism and methionine formation is the methylene tetrahydrofolate reductase enzyme (MTHFR), which is present mainly in the liver and kidney. It is responsible for the conversion of 5,10- methylene tetrahydrofolate to 5-methyl tetrahydrofolate. (12)

 Genetic polymorphisms of the folic acid cycle key enzymes have been implicated in idiopathic male sterility. Folic acid metabolism seems to be of great value in intact male fertility process. Any detected defects in the folic acid metabolism may participate in wide metabolic functions.(12)

The MTHFR C677T gene single nucleotide polymorphism (SNP) may influence the folic acid metabolic pathway and may cause hyperhomocysteinemia.

Elevated homocysteine levels may have broad pathological drawbacks and it has been reported to be involved in intrauterine fetal death in pregnant women (13). MTHFR C677T gene SNP may influence the spermatogenesis process via regulation of the DNA methylation. Moreover, methionine compound is essential in formation of 5- adenosyl methionine which is a methyl group donor to cytosine and lysine in the DNA and histones which participate in the DNA formation and gene regulation.(13)

 

        Till now there are not enough studies examining the role of that SNP in male infertility. We designed this experimental study to examine the MTHFR C677T SNP and its association with male infertility in rats.  Moreover, we will investigate effect of folic acid intake its effect on the spermatogenesis with those MTHFR C677T SNP and CC genotype carriers in animal model study.