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Article

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

by 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2 and 1,2,3,*
1
Department of Nutrition and Food Hygiene, School of Public Health, Peking University, NO.38 Xueyuan Road, Beijing 100083, China
2
PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, NO.38 Xueyuan Road, Beijing 100083, China
3
Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, NO.38 Xueyuan Road, Beijing 100083, China
*
Author to whom correspondence should be addressed.
Academic Editor: Michael Freemark
Nutrients 2021, 13(10), 3644; https://doi.org/10.3390/nu13103644
Received: 29 September 2021 / Revised: 15 October 2021 / Accepted: 15 October 2021 / Published: 18 October 2021
(This article belongs to the Special Issue Nutrition and Metabolism in the First 1,000 Days of Life)
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. View Full-Text
Keywords: metabolic profiles; gestational diabetes mellitus; untargeted metabolism analysis metabolic profiles; gestational diabetes mellitus; untargeted metabolism analysis
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MDPI and ACS Style

Zhou, Y.; Zhao, R.; Lyu, Y.; Shi, H.; Ye, W.; Tan, Y.; Li, R.; Xu, Y. Serum and Amniotic Fluid Metabolic Profile Changes in Response to Gestational Diabetes Mellitus and the Association with Maternal–Fetal Outcomes. Nutrients 2021, 13, 3644. https://doi.org/10.3390/nu13103644

AMA Style

Zhou Y, Zhao R, Lyu Y, Shi H, Ye W, Tan Y, Li R, Xu Y. Serum and Amniotic Fluid Metabolic Profile Changes in Response to Gestational Diabetes Mellitus and the Association with Maternal–Fetal Outcomes. Nutrients. 2021; 13(10):3644. https://doi.org/10.3390/nu13103644

Chicago/Turabian Style

Zhou, Yalin, Runlong Zhao, Ying Lyu, Hanxu Shi, Wanyun Ye, Yuwei Tan, Rui Li, and Yajun Xu. 2021. "Serum and Amniotic Fluid Metabolic Profile Changes in Response to Gestational Diabetes Mellitus and the Association with Maternal–Fetal Outcomes" Nutrients 13, no. 10: 3644. https://doi.org/10.3390/nu13103644

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