Influence of pregnancy and non-fasting conditions on the plasma metabolome in a rat prenatal toxicity study

• Published in: Archives of toxicology 2021-09, Vol.95 (9), p.2941-2959
• Main Authors: Ramirez-Hincapie, S., Giri, V., Keller, J., Kamp, H., Haake, V., Richling, E., van Ravenzwaay, B.
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - blood; Animals; Biomedical and Life Sciences; Biomedicine; Body weight; Chromatography, Liquid; Diet; Environmental Health; Fasting; Fatty acids; Fatty Acids - blood; Female; Food; Food consumption; Gas Chromatography-Mass Spectrometry; Glucose - metabolism; Hormones; Ketone Bodies - metabolism; Ketones; Laboratory testing; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolome - physiology; Metabolomics; Metabolomics - methods; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Plasma; Pregnancy; Pregnancy - metabolism; Rats; Rats, Wistar; Reproductive Toxicology; Tandem Mass Spectrometry; Toxicity; Triglycerides; Triglycerides - blood
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-021-03105-0

The current parameters for determining maternal toxicity (e.g. clinical signs, food consumption, body weight development) lack specificity and may underestimate the extent of effects of test compounds on the dams. Previous reports have highlighted the use of plasma metabolomics for an improved and mechanism-based identification of maternal toxicity. To establish metabolite profiles of healthy pregnancies and evaluate the influence of food consumption as a confounding factor, metabolite profiling of rat plasma was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. Metabolite changes in response to pregnancy, food consumption prior to blood sampling (non-fasting) as well as the interaction of both conditions were studied. In dams, both conditions, non-fasting and pregnancy, had a marked influence on the plasma metabolome and resulted in distinct individual patterns of changed metabolites. Non-fasting was characterized by increased plasma concentrations of amino acids and diet related compounds and lower levels of ketone bodies. The metabolic profile of pregnant rats was characterized by lower amino acids and glucose levels and higher concentrations of plasma fatty acids, triglycerides and hormones, capturing the normal biochemical changes undergone during pregnancy. The establishment of metabolic profiles of pregnant non-fasted rats serves as a baseline to create metabolic fingerprints for prenatal and maternal toxicity studies.