Enthoven Luke F, Shi Yuanyuan, Fay Emily E, Moreni Sue, Mao Jennie, Honeyman Emma M, Smith Chase K, Whittington Dale, Brockerhoff Susan E, Isoherranen Nina, Totah Rheem A, Hebert Mary F
Department of Pharmacy, University of Washington, Seattle, WA 98195, USA.
Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Metabolites. 2023 Feb 7;13(2):242. doi: 10.3390/metabo13020242.
Limited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18-50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again ≥3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis ( = 2 × 10 and FDR = 1 × 10), valine, leucine, and isoleucine metabolism ( = 2 × 10 and FDR = 2 × 10), and xanthine metabolism ( = 4 × 10 and FDR = 4 × 10). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy.
关于妊娠对母体代谢组影响的数据有限。因此，本研究的目的是使用代谢组学分析来确定受妊娠影响的途径，随后进行靶向验证分析，以得出关于妊娠期间代谢改变的更有力结论。本研究纳入了47名年龄在18至50岁之间的孕妇，每位受试者均作为自身对照。在妊娠25至28周期间以及产后≥3个月时采集血浆样本，用于代谢组学分析，采用亲水相互作用液相色谱/超高效液相色谱/串联质谱法（HILIC/UHPLC/MS/MS），并利用液相色谱/质谱法对10种显著改变的氨基酸进行靶向特定浓度验证分析。对代谢组学数据进行主成分分析（PCA），在初步评估中清晰地分离了妊娠组和产后组，并识别出异常值。在记录的980种代谢物中，有706种在妊娠和产后之间存在显著差异。通路分析显示有三条显著受影响的通路，精氨酸生物合成（P = 2×10⁻⁴，错误发现率FDR = 1×10⁻³）、缬氨酸、亮氨酸和异亮氨酸代谢（P = 2×10⁻⁴，FDR = 2×10⁻³）以及黄嘌呤代谢（P = 4×10⁻⁴，FDR = 4×10⁻³）。由于它们在临床方面的重要性以及在氨基酸代谢中的相互关联作用，我们将分析重点放在精氨酸生物合成和支链氨基酸（BCAA）代谢上。在验证分析中，10种代谢物中有7种被确认为显著，并且所有10种都证实了代谢组学分析中观察到的浓度变化方向。数据支持妊娠期间尿素氮处置和氨基酸代谢的改变。这些变化也可能影响内源性一氧化氮的产生，并导致妊娠相关疾病。本研究为妊娠期间氨 - 尿素氮和BCAA代谢的变化提供了证据。
