J Proteome Res 2011 Oct;10 (10): 4845-54. [IF:5.460]
Metabolic signature of pregnant women with neural tube defects in offspring.
Zheng X , Su M , Pei L , Zhang T , Ma X , Qiu Y , Xia H , Wang F , Zheng X , Gu X , Song X , Li X , Qi X , Chen G , Bao Y , Chen T , Chi Y , Zhao A , Jia W .
WHO Collaborating Center for Reproductive Health and Population Science, Beijing, PR China.
北京大学世卫组织生殖健康和人口科学合作中心
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 300000 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.
摘要
神经管缺陷后代孕妇以前还没有其特征。在本文中, 我们报告一项剖析研究，对吕梁县的101例受到神经管缺陷后代影响的孕妇与143例正常妊娠结局的孕妇的血清代谢组的特征进行比较，吕梁县是中国神经管缺陷出生率最流行的地区。一个血清代谢组学研究还进行了确定显著改变与di-n-butyl代谢物(DBP)引起的小鼠畸形发生有关的代谢分子。在孕妇神经管缺陷代谢信号以线粒体呼吸,神经递质γ-氨基丁酸、蛋氨酸循环为特征。有趣的是，来自小鼠DBP诱导的畸形发生的一致发现表明琥珀酸增加了和延胡索酸减少了，意味着抑制的脱氢酶在缺陷的线粒体有一定的关系。母亲的新陈破坏特征提供了对潜在人类神经管缺陷的代谢机制以及可能的预防措施的深刻理解。
