Chronic maternal cortisol excess during late gestation leads to metabolic alterations in the newborn heart.
Chronic maternal cortisol excess during late gestation leads to metabolic alterations in the newborn heart.
复制标题
DOI：
10.1152/ajpendo.00386.2018
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Jacquelyn M. Walejko;Andrew T. Antolic;J. Koelmel;T. Garrett;A. Edison;M. Keller‐Wood
中科院分区：
文献类型：
--
作者：
Jacquelyn M. Walejko;Andrew T. Antolic;J. Koelmel;T. Garrett;A. Edison;M. Keller‐Wood
我们实验室先前在一个绵羊妊娠模型中表明，妊娠晚期母体皮质醇异常升高会导致围产期胎儿心律失常增加和死亡率上升。此外，对胎儿心脏的转录组分析表明，在子宫内暴露于过量皮质醇的动物中，三羧酸（TCA）循环中间产物和脂质代谢物发生了改变。因此，我们利用绵羊妊娠模型来确定母体皮质醇的慢性升高如何在出生前改变母体和胎儿血清，以及在足月时改变新生儿心脏代谢物和脂质。从妊娠第115天开始，母羊要么接受1mg·kg⁻¹·day⁻¹的皮质醇输注（n = 9），要么不接受处理（n = 6）。在妊娠第125天从母体和胎儿采集血清，并在出生后采集心脏。进行质子核磁共振（¹H - NMR）光谱分析以测量新生儿心脏标本以及胎儿和母体血清标本的代谢谱。进行质谱分析以测量新生儿心脏标本的脂质谱。我们观察到在妊娠晚期母体皮质醇过量后，新生儿心脏的氨基酸和TCA循环代谢以及脂质和甘油磷脂代谢发生了改变。此外，我们观察到在妊娠晚期胎儿血清（而非母体血清）中的氨基酸和TCA循环代谢物发生了改变。这些结果表明，胎儿暴露于过量的母体皮质醇会在出生前改变胎盘和胎儿的代谢，并限制心脏代谢的正常成熟，这可能导致在这些动物中观察到的围产期心律失常风险增加，或者导致日后的心肌病。
Our laboratory has previously shown in an ovine model of pregnancy that abnormal elevations in maternal cortisol during late gestation lead to increased fetal cardiac arrhythmias and mortality during peripartum. Furthermore, transcriptomic analysis of the fetal heart suggested alterations in TCA cycle intermediates and lipid metabolites in animals exposed to excess cortisol in utero. Therefore, we utilized a sheep model of pregnancy to determine how chronic increases in maternal cortisol alter maternal and fetal serum before birth and neonatal cardiac metabolites and lipids at term. Ewes were either infused with 1 mg·kg-1·day-1 of cortisol starting at gestational day 115 ( n = 9) or untreated ( n = 6). Serum was collected from the mother and fetus (gestational day 125), and hearts were collected following birth. Proton nuclear magnetic resonance (1H-NMR) spectroscopy was conducted to measure metabolic profiles of newborn heart specimens as well as fetal and maternal serum specimens. Mass spectrometry was conducted to measure lipid profiles of newborn heart specimens. We observed alterations in amino acid and TCA cycle metabolism as well as lipid and glycerophospholipid metabolism in newborn hearts after excess maternal cortisol in late gestation. In addition, we observed alterations in amino acid and TCA cycle metabolites in fetal but not in maternal serum during late gestation. These results suggest that fetal exposure to excess maternal cortisol alters placental and fetal metabolism before birth and limits normal cardiac metabolic maturation, which may contribute to increased risk of peripartum cardiac arrhythmias observed in these animals or later life cardiomyopathies.