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J Proteome Res. 2011 Oct 7;10(10):4845-54. doi: 10.1021/pr200666d. Epub 2011 Sep 22.

Metabolic signature of pregnant women with neural tube defects in offspring.

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1
WHO Collaborating Center for Reproductive Health and Population Science, Beijing, PR China.

Abstract

Neural tube defects (NTDs) are one of the most common types of birth defects, affecting approximately 1 of every 1000 pregnancies in the United States and an estimated 300 000 newborns worldwide each year. The metabolic signature of pregnant women with NTDs in offspring has not previously been characterized. In this paper, we report a profiling study that characterized the serum metabolome of 101 pregnant women affected with NTDs in offspring in comparison with 143 pregnant women with normal pregnancy outcomes in Lvliang prefecture, the area with the highest birth prevalence of NTDs in China. A serum metabonomic study was also conducted to identify significantly altered metabolites associated with di-n-butyl phthalate (DBP)-induced teratogenesis in mice. The metabolic signature of NTD in pregnant women is characterized by the impaired mitochondrial respiration, neurotransmitter γ-aminobutyric acid, and methionine cycle. Of interest, consistent findings from DBP-induced teratogenesis in mice demonstrated increased succinate and decreased fumarate, suggesting an inhibited succinic dehydrogenase implicated in the defective mitochondria. The characteristic disruption of maternal metabolism offers important insights into metabolic mechanisms underlying human NTDs as well as potential preventive strategies.

PMID:
21902205
DOI:
10.1021/pr200666d
[Indexed for MEDLINE]

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