A metabolomic study on the gender-dependent effects of maternal exposure to fenvalerate on neurodevelopment in offspring mice

摘要

Background: The general population is widely exposed to fenvalerate. However, the effects of maternal exposure to fenvalerate on neurodevelopment in offspring and the underlying metabolic mechanism are largely unknown. Methods: Pregnant mice were exposed to fenvalerate for 11 consecutive days. The forced swimming test (FST) was performed in 35 day-old offspring to investigate the effects of fenvalerate on neurobehavioral responses. Blood serum free T4 and free T3 concentrations were measured using commercial EUSA. Blood and thyroid samples were used for metabolomic analyses with UPLC Q-Exactive. The expression levels of neurotransmitter metaolite receptors were determined in the frontal cortex of offspring using real-time PCR. Results: The immobility time, free T4 and free T3, and expression levels of Htrla and Htr2a were statistically changed in offspring male mice. Metabolomic analysis revealed that the pentose phosphate pathway, starch and sucrose metabolism, glutamic acid metabolism were the key changed pathways in the blood, and thiamine metabolism was the key changed pathway in the thyroid. Conclusion: Prenatal exposure to fenvalerate affected neurodevelopment in male offspring mice both via the changed abundances of metabolites involved in glycolysis related metabolism and medium-chain fatty acid metabolism, and the changes in 5-HT receptor expression.