Hyperhomocysteinemia is not sufficient to cause preeclampsia in an animal model: the importance of folate intake

OBJECTIVE: The objective of our study was to determine whether methylenetetrahydrofolate reductase (Mthfr)-deficient mice develop preeclampsia (PE). STUDY DESIGN: Mice were placed on a normal or low-folate/high-methionine (LF/HM) diet to assess the impact of mild and severe homocysteinemia. Blood pressure and proteinuria were measured throughout gestation in Mthfr-deficient and control mice on both diets, by radiotelemetry and by determining the urinary albumin/creatinine ratio by enzyme-linked immunosorbent assay, respectively. RESULTS: Although Mthfr-deficient mice have endothelial dysfunction, they do not develop hypertension or proteinuria during gestation. The LF/HM diet induced proteinuria, growth restriction, and a decrease in the number of pups per litter in all mice without any effect on the placenta. CONCLUSION: Our study clearly demonstrates that hyperhomocysteinemia is not sufficient to cause PE in this animal model. Furthermore, it confirms the importance of folate intake on pregnancy outcomes.