Homocysteine and human reproduction.

Homocysteine is an amino acid that is capable of disturbing the proper growth of cells. Hyperhomocysteinemia can lead to a non-closure of the neural tube. The underlying basis is a derangement of homocysteine metabolism due to a missense mutation of the MTHFR enzyme that has to catalyze the folate metabolic cycle furnishing sufficient methyl groups for DNA and tRNA synthesis. Folate can overcome the dysfunction of the mutation and the decreased activity of the thermolabile MTHFR. Homocysteine is also recognized as an independent risk factor for obstetrical vascular disease that can manifest itself in maternal veins (thrombosis), arteries (preeclampsia) or spiral arteries supplying the placenta (placental abruption). Low vitamin status (folic acid, vitamin B6 and B12), hyperhomocysteinemia, the MTHFR gene mutation C677T, and thrombotic factors like Protein C, Protein S. antithrombin III, factor V Leiden and Activated Protein C, are alone or in combination high risk factors for obstetrical vascular disease. Their values can be modulated by B-vitamin status and could be able to prevent disease from occurring or recurring. Placebo-randomized trials have been done in neural tube defects but are urgently needed in the vascular area. The common denominator of the effect of homocysteine on the embryo and the blood vessels (endothelium) could be sited in the process of proliferation of cells that need proper methyl groups for proper function.