Department of Pediatrics, University of Washington, Seattle, Washington, USA.
Pediatr Res. 2012 Apr;71(4 Pt 1):338-44. doi: 10.1038/pr.2011.74. Epub 2012 Feb 15.
The fetal-to-neonatal transition is one of the most complex processes in biological existence; much is unknown about this transition on the molecular and biochemical level. Based on growing metabolomics literature, we hypothesize that metabolomic analysis will reveal the key biochemical intermediates that change during the birth transition.
Using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS), we identified 100 metabolites that changed during this transition. Of these 100 metabolites, 23 demonstrated significant change during the first 72 h. Of note, four intermediates of the tricarboxylic acid (TCA) cycle were identified (α-ketoglutaric acid, fumaric acid, malic acid, and succinyl-CoA), demonstrating a consistent rate of rise during the study. This may signify the transition of the neonate from a hypoxic in utero environment to an oxygen-rich environment. Important signaling molecules were also identified, including myo-inositol and glutamic acid.
GC × GC-TOFMS was able to identify important metabolites associated with metabolism and signaling. These data can be used as a baseline for normal birth transition, which may aid in future perinatal research investigations.
Late-preterm Macaca nemestrina were delivered by hysterotomy, with plasma drawn from the cord blood and after birth at eight additional time points to 72 h of age.
胎儿向新生儿的过渡是生物存在中最复杂的过程之一;在分子和生化水平上,人们对这一过渡知之甚少。基于不断增长的代谢组学文献,我们假设代谢组学分析将揭示出生过渡过程中发生变化的关键生化中间产物。
使用二维气相色谱与飞行时间质谱联用(GC×GC-TOFMS),我们鉴定出 100 种在这一过渡过程中发生变化的代谢物。在这 100 种代谢物中,有 23 种在最初的 72 小时内发生了显著变化。值得注意的是,鉴定出了三羧酸(TCA)循环的四个中间产物(α-酮戊二酸、富马酸、苹果酸和琥珀酰辅酶 A),在研究过程中它们的上升速度一致。这可能表明新生儿从宫内缺氧环境过渡到富含氧气的环境。还鉴定出了重要的信号分子,包括肌醇和谷氨酸。
GC×GC-TOFMS 能够鉴定出与代谢和信号有关的重要代谢物。这些数据可以作为正常分娩过渡的基线,可能有助于未来围产期研究的调查。
通过剖腹术分娩晚期早产猕猴,从脐带血和出生后 8 个额外时间点抽取血浆,直到出生后 72 小时。