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Abstract

Review Article

Detrimental Effects of Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism on Human Reproductive Health: A Review

Vandana Rai* and Pradeep Kumar

Published: 05 March, 2025 | Volume 8 - Issue 1 | Pages: 007-014

Methylenetetrahydrofolate Reductase (MTHFR) is an important enzyme of the folate cycle, which is required to convert 5,10-methyltetrahydrofolate into 5-methyltetrahydrofolate (5-methylTHHF). 5-methyl THF is a methyl group donor for several cellular methylation processes. It also donates methyl group for the conversion of homocysteine into methionine, the higher concentration of which is toxic. MTHFR gene C677T polymorphism is clinically important polymorphism and the variant MTHFR (A222V) enzyme has reduced activity, hence increasing the requirement for folic acid. Less conversion of folate to 5-methyl-THF due to C677T polymorphism results in a higher plasma concentration of homocysteine (hyperhomocysteinemia). Individuals having C677T polymorphism are susceptible to various diseases, including reproductive problems like male infertility, polycystic ovary syndrome, Recurrent Pregnancy Loss (RPL), Preeclampsia (PE), placental abruption, and adverse pregnancy outcomes. MTHFR C677T polymorphism mimics folate deficiency, and folate is required for DNA synthesis, repair, methylation, and proper chromosome segregation, and all these processes are important for foetal growth and normal development. Methylation and demethylation processes control the gene expression of about 45% of human genes. Impaired methylation influences the expression of genes involved in the regulation of hormones, spermatogenesis, and oogenesis. In males, oxidative stress damages sperm DNA decreases sperm motility, and may impair fertilization capability. In pregnant women, hyperhomocysteinemia increases oxidative stress and inflammation within the placenta, which causes damage to placental tissue, impairs its function, and disrupts foetal development. Further, hyperhomocysteinemia (HHcy) is embryotoxic and neurotoxic and is responsible for congenital anomalies in the foetus. This review supports the idea that MTHFR C677T polymorphism is associated with an increased risk for male infertility, PCOS, RPL, PE, and congenital anomalies. This review may provide a clue toward a better understanding of the correlation between the MTHFR C677T polymorphism and its detrimental effects on human reproductive health.

Read Full Article HTML DOI: 10.29328/journal.cjog.1001182 Cite this Article Read Full Article PDF

Keywords:

MTHFR; Folate; Homocysteine; Male infertility; Preeclampsia; PCOS; Congenital anomalies

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Assistant Professor, UCLAS Uttaranchal University, Dehradun, India

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University of Agriculture, Pakistan

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Leonid Feldman

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Eastern Mediterranean University, Cyprus

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Ekiti State University, Nigeria

Adebukola Ajite

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Atsedemariam Andualem

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BS, PharmD., MBA, CPHIMS, FHIMSS, Adjunct Professor, Global Healthcare Management, MCPHS University, Chief Strategy Offi cer, MedicaSoft, Senior Advisor, National Health IT (NHIT) Collaborative for Underserved, New York HIMSS, National Liaison, Health 2.0 Boston, Past Chair, Chair Innovation, USA

Helen Figge

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Ph.D, Boston University Department of Communication Sciences and Disorders and Knowledge Research Institute, Inc., 2131 Reflection Bay Drive, Arlington, Texas 76013, USA

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Palestine College of Nursing, Khan Younis, Gaza Strip, Palestine

Ayman M Abu Mustafa

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Department of Agricultural Economics, Agribusiness and Extension, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Akowuah Jones Asafo

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