Michelle Broekhuizen, Heike Allenberg, Claude P van der Ley, Sofie K M van Zundert, Zongye Cai, Martijn van Faassen, Daphne Merkus, A H Jan Danser, Anja Lange, Irwin K M Reiss, Matthias Heckmann
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引用次数: 0
Abstract
Background: Tryptophan and its kynurenine pathway (KP) metabolites play key roles in modulating the immune system and vasculature, and exhibit both pro- and antioxidant properties, making them crucial for a healthy pregnancy and fetal development. Disruptions in the KP may impact both prenatal and postnatal health, however, data on fetal KP metabolite concentrations and their alterations in pregnancy-related disorders remain scarce. This study aims to investigate the association between pregnancy complications and KP metabolite concentrations in umbilical cord blood.
Methods: Pregnancies complicated by preeclampsia (n = 40), fetal growth restriction (FGR, n = 33), pregestational diabetes mellitus (DM, n = 42), gestational diabetes mellitus (GDM, n = 61), and amniotic infection syndrome (AIS, n = 47) were included, along with 410 controls matched in a 1:2 ratio using Mahalanobis nearest-neighbor matching from a prospective birth cohort study. Tryptophan, kynurenine, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, and nicotinic acid were measured in umbilical cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differences in metabolite concentrations were analyzed using unpaired t-tests and linear regression models to control for potential confounders.
Results: Tryptophan concentrations were decreased in cases of preeclampsia and DM. We identified elevated levels of 3-hydroxykynurenine in preeclampsia, kynurenine in GDM, and nicotinic acid in both FGR and DM. Quinolinic acid levels were also higher in preeclampsia and GDM, although this was not significant after adjusting for confounding variables. We observed no changes in KP metabolites in AIS.
Conclusion: This study identified distinct alterations in umbilical cord blood KP metabolite concentrations in pregnancies with preeclampsia, FGR, DM, and GDM, but not AIS. This suggests differential regulation and activation of the KP depending on the pregnancy disorder. Such changes may influence maternal and infant health and could play a role in fetal programming, with potential long-term effects on child development and health.
背景：色氨酸及其犬尿氨酸途径（KP）代谢物在调节免疫系统和血管系统中发挥关键作用，并表现出促氧化和抗氧化特性，对健康妊娠和胎儿发育至关重要。KP的破坏可能会影响产前和产后健康，然而，关于胎儿KP代谢物浓度及其在妊娠相关疾病中的变化的数据仍然很少。本研究旨在探讨妊娠并发症与脐带血KP代谢物浓度之间的关系。方法：纳入合并先兆子痫（n = 40）、胎儿生长受限（FGR, n = 33）、妊娠期糖尿病（DM, n = 42）、妊娠期糖尿病（GDM, n = 61）和羊膜感染综合征（AIS, n = 47）的妊娠，并采用前瞻性出生队列研究中马氏最近邻匹配，按1:2比例匹配410例对照。采用液相色谱-串联质谱法（LC-MS/MS）测定脐带血中色氨酸、犬尿氨酸、邻氨基苯甲酸、3-羟基犬尿氨酸、3-羟基犬尿氨酸、犬尿氨酸、黄嘌呤酸、喹啉酸、吡啶酸和烟酸的含量。使用非配对t检验和线性回归模型分析代谢物浓度的差异，以控制潜在的混杂因素。结果：色氨酸浓度在子痫前期和糖尿病中降低。我们发现3-羟基犬尿氨酸水平在子痫前期升高，犬尿氨酸水平在GDM中升高，烟酸水平在FGR和DM中升高。喹啉酸水平在子痫前期和GDM中也升高，尽管在调整混杂变量后这并不显著。我们观察到AIS患者KP代谢物没有变化。结论：本研究确定了子痫前期、FGR、DM和GDM孕妇脐带血KP代谢物浓度的明显变化，但没有发现AIS。这表明，根据妊娠障碍，KP的调节和激活存在差异。这些变化可能影响孕产妇和婴儿的健康，并可能在胎儿规划中发挥作用，对儿童发育和健康产生潜在的长期影响。
期刊介绍：
Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences.
The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
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