期刊
MOLECULAR GENETICS AND METABOLISM
卷 94, 期 3, 页码 336-342出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2008.03.004
关键词
folate methionine; congenital heart defects; pregnancy complications; reproductive outcome
资金
- NIGMS NIH HHS [R01 GM024908-28] Funding Source: Medline
Low dietary folate and polymorphisms in genes of folate metabolism can influence risk for pregnancy complications and birth defects. Methionine synthase reductase (MTRR) is required for activation of methionine synthase, a folate- and vitamin B-12-dependent enzyme. A polymorphism in MTRR (p.122M), present in the homozygous state in 25% of many populations, may increase risk for neural tube defects. To examine the impact of MTRR deficiency on early development and congenital heart defects, we used mice harboring a gene-trapped (gt) allele in Mtrr. Female mice (Mtrr(+/+), Mtrr(+/gt), and Mtrr(gt/gt)) were mated with male Mtrr(+/g) mice. Reproductive outcomes and cardiac phenotype (presence of defects and myocardial thickness) were assessed at E14.5. Mtrr-deficient mothers had more resorptions and more delayed embryos per litter (resorptions per litter: 0.29 +/- 0.13; 1.21 +/- 0.41; 1.87 +/- 0.38 and delayed embryos per litter: 0.07 +/- 0.07; 0.14 +/- 0.14; 0.60 +/- 0.24 in Mtrr(+/+), Mtrr(+/gt), and Mtrr(gt/gt) mothers respectively). Placentae of Mtrr(gt/gt) mothers were smaller and their embryos were smaller, with myocardial hypoplasia and a higher incidence of ventricular septal defects (VSD) per litter (0; 0.57 +/- 0.30; 1.57 +/- 0.67 in Mtrr(+/+), Mtrr(+/gt), and Mtrr(gt/gt) groups respectively). Embryonic Mtrr(gt/gt) genotype was associated with reduced embryonic length, reduced embryonic and placental weight, and higher incidence of VSD, but did not affect myocardial thickness or embryonic delay. We conclude that Mtrr deficiency adversely impacts reproductive outcomes and cardiac development in mice. These findings may have implications for nutritional prevention of heart defects, particularly in women with the common MTRR polymorphism.
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