Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics, and of expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm and cardiac muscle. The present studies were designed to test for effects of chronically increased maternal cortisol on gene expression and metabolomics in placentomes near term. We hypothesized that changes in placenta may underlie or contribute to the alterations in fetal serum metabolomics, and thereby contribute to changes in striated muscle metabolism. Placentomes were collected from pregnancies in early labor (143±1 d gestation) of control ewes (n=7) or ewe treated with cortisol (1 mg/kg/d iv; n=5) starting at day 115 of gestation. Transcriptomics and metabolomics were performed using an ovine gene expression microarray (Agilent 019921) and HR-MAS NMR, respectively. Multi-omic analysis indicates that amino acid metabolism, particularly of branched chain amino acids and glutamate occur in placenta; changes in amino acid metabolism, degradation or biosynthesis in placenta were consistent with changes in valine, isoleucine, leucine and glycine in fetal serum. The analysis also indicates changes in glycerophospholipid metabolism and suggests changes in ER stress and antioxidant status in the placenta. These findings suggest that changes in placental function occurring with excess maternal cortisol in late gestation may contribute to metabolic dysfunction in the fetus at birth.

中文翻译：

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母体高皮质醇血症改变绵羊胎盘代谢：多组学观点。

先前的研究表明，孕晚期母体皮质醇或母体压力的增加会增加足月死产的风险。在妊娠最后 0.20 年母体皮质醇增加的绵羊模型中，我们之前发现了胎儿血清和心脏代谢组学中断的证据，以及与股二头肌、横膈膜和心肌中线粒体功能和代谢相关的基因表达的证据。本研究旨在测试长期增加的母体皮质醇对近期胎盘基因表达和代谢组学的影响。我们假设胎盘的变化可能是胎儿血清代谢组学变化的基础或促成因素，从而导致横纹肌代谢的变化。从对照母羊（n=7）或用皮质醇（1mg/kg/d iv；n=5）处理的母羊的早期分娩（妊娠143±1 d）的妊娠中收集胎盘，从妊娠第115天开始。转录组学和代谢组学分别使用绵羊基因表达微阵列 (Agilent 019921) 和 HR-MAS NMR 进行。多组学分析表明，胎盘存在氨基酸代谢，尤其是支链氨基酸和谷氨酸代谢；胎盘中氨基酸代谢、降解或生物合成的变化与胎儿血清中缬氨酸、异亮氨酸、亮氨酸和甘氨酸的变化一致。该分析还表明甘油磷脂代谢的变化，并表明胎盘中内质网应激和抗氧化状态的变化。