Cyclophosphamide Induces Lipid and Metabolite Perturbation in Amniotic Fluid during Rat Embryonic Development

Cyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of...

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Bibliographic Details
Published in:Metabolites 2022-11, Vol.12 (11), p.1105
Main Authors: Xu, Jianya, Fang, Huafeng, Chong, Ying, Lin, Lili, Xie, Tong, Ji, Jianjian, Shen, Cunsi, Shi, Chen, Shan, Jinjun
Format: Article
Language:English
Subjects:
Acids
Amniotic fluid
Analysis
Biomarkers
Chromatography
Complications and side effects
Critical period
Cyclophosphamide
Embryogenesis
Embryonic development
Embryos
embryotoxicity
Evaluation
Females
Fetuses
Growth
Laboratory animals
Lecithin
Lipid metabolism
lipidomics
Lipids
Mass spectrometry
Metabolism
Metabolites
Oxidative stress
Patient outcomes
Phosphatidylcholine
Placenta
Polyunsaturated fatty acids
Properties
Rats
Rattus
Scientific imaging
Sphingomyelin
Teratogenicity
Toxicants
Toxicity
Triglycerides
Tryptophan
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Summary:Cyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of CP on the lipid and metabolic profiles of amniotic fluid was evaluated using a UHPLC-Q-Exactive Orbitrap MS-based method. Metabolome analysis was performed using the MS-DIAL software with LipidBlast and NIST. Initially, we identified 636 and 154 lipid compounds in the positive and negative ion modes and 118 metabolites for differential analysis. Mainly 4 types of oxidized lipids in the amniotic fluid were found to accumulate most significantly after CP treatment, including very-long-chain unsaturated fatty acids (VLCUFAs), polyunsaturated fatty acid (PUFA)-containing triglycerides (TGs), oxidized phosphatidylcholine (PC), and sphingomyelin (SM). Tryptophan and some long-chain saturated fatty acids were lowered pronouncedly after CP treatment. These findings suggest that CP may exert teratogenic toxicity on pregnant rats through maternal and fetal oxidative stress. The UHPLC-Q-Exactive Orbitrap MS-based lipidomics approach is worthy of wider application for evaluating the potential toxicity of other agents (toxicants) during embryonic development.
ISSN:2218-1989
2218-1989
DOI:10.3390/metabo12111105