Serum and Amniotic Fluid Metabolic Profile Changes in Response to Gestational Diabetes Mellitus and the Association with Maternal–Fetal Outcomes

Abstract

This study was designed to identify serum and amniotic fluid (AF) metabolic profile changes in response to gestational diabetes mellitus (GDM) and explore the association with maternal–fetal outcomes. We established the GDM rat models by combining a high-fat diet (HFD) with an injection of low-dose streptozotocin (STZ), detected the fasting plasma glucose (FPG) of pregnant rats in the second and third trimester, and collected AF and fetal rats by cesarean section on gestational day 19 (GD19), as well as measuring the weight and crown–rump length (CRL) of fetal rats. We applied liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the untargeted metabolomics analyses of serum and AF samples and then explored their correlation with maternal–fetal outcomes via the co-occurrence network. The results showed that 91 and 68 metabolites were upregulated and 125 and 78 metabolites were downregulated in serum and AF samples exposed to GDM, respectively. In maternal serum, the obvious alterations emerged in lipids and lipid-like molecules, while there were great changes in carbohydrate and carbohydrate conjugates, followed by amino acids, peptides, and analogs in amniotic fluid. The altered pathways both in serum and AF samples were amino acid, lipid, nucleotide, and vitamin metabolism pathways. In response to GDM, changes in the steroid hormone metabolic pathway occurred in serum, and an altered carbohydrate metabolism pathway was found in AF samples. Among differential metabolites in two kinds of samples, there were 34 common biochemicals shared by serum and AF samples, and a mutual significant association existed. These shared differential metabolites were implicated in several metabolism pathways, including choline, tryptophan, histidine, and nicotinate and nicotinamide metabolism, and among them, N1-methyl-4-pyridone-3-carboxamide, 5’-methylthioadenosine, and kynurenic acid were significantly associated with both maternal FPG and fetal growth. In conclusion, serum and AF metabolic profiles were remarkably altered in response to GDM. N1-Methyl-4-pyridone-3-carboxamide, 5’-methylthioadenosine, and kynurenic acid have the potential to be taken as biomarkers for maternal–fetal health status of GDM. The common and inter-related differential metabolites both in the serum and AF implied the feasibility of predicting fetal health outcomes via detecting the metabolites in maternal serum exposed to GDM.

Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction

“…Among them, p-synephrine and N1-methyl-4-pyridone-3-carboxamide were upregulated, while ginkgolide C was decreased in FGR patients. Consistent with our findings, N1-methyl-4-pyridone-3-carboxamide has been detected in serum and amniotic fluid samples in gestational diabetes mellitus (GDM) patients ( 35 ). Furthermore, a negative correlation between N1-methyl-4-pyridone-3-carboxamide and fetal weight has been reported in those patients involved in nicotinate and nicotinamide metabolism ( 35 ).…”

“…Consistent with our findings, N1-methyl-4-pyridone-3-carboxamide has been detected in serum and amniotic fluid samples in gestational diabetes mellitus (GDM) patients ( 35 ). Furthermore, a negative correlation between N1-methyl-4-pyridone-3-carboxamide and fetal weight has been reported in those patients involved in nicotinate and nicotinamide metabolism ( 35 ). A recent study showed that ginkgolide C might promote intestinal barrier function and exert anti-inflammatory effects by inhibiting the nuclear factor kappa-light-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in a dextran sulfate sodium-induced colitis model ( 36 ).…”

Acute Fetal Metabolomic Changes in Twins Undergoing Fetoscopic Surgery for Twin-Twin Transfusion Syndrome

“…It thus is quite biologically plausible that the surgical stress of FLP and the major fluid shifts occurring during the lasering of the placenta would lead to increased consumption of alternative energy sources for the fetus, and the metabolomic profiling in this study captures that acute strain on fetal metabolism. Other high VIP score metabolites, such as choline, are known to play key roles in proper fetal growth and alterations in fetal glucose lead to abnormalities in choline metabolism (Zhou et al, 2021). While amniotic fluid lactate has not been scrutinized during fetal surgery, there has been study of amniotic fluid lactate during labor and specifically abnormal labor.…”

Influence of induced diabetes mellitus on hormonal profile of Lewis lung carcinoma in BALB/c Nude mice

“…При этом злокачественная опухоль на фоне СД развивалась гораздо быстрее, нежели в самостоятельном варианте, объемы опухолей нарастали стремительно, продолжительность жизни у самок была меньше. Экспериментальные исследования гестационного диабета показали, что в ответ на внутриутробную среду с высоким содержанием глюкозы плод претерпевает ряд адаптивных изменений, таких как ускорение катаболизма и утилизации глюкозы, что влияет на его рост и развитие [12]. Проводя некоторую параллель между ростом злокачественной опухоли и беременностью, когда как при физиологическом, так и при патологическом процессах происходит «охрана чужого в своем», можно предположить, что злокачественная опухоль, получая дополнительные ресурсы глюкозы, могла существенно ускорить свой пролиферативный потенциал.…”