Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation

•We demonstrate embryonic cell processes that are altered by homocysteine and lithium.•Bioinformatics analysis show processes primarily changed relate to lipid metabolism.•The lipid metabolic changes are dependent on the gender of the embryo.•The transcriptome of male embryos are more altered than o...

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Bibliographic Details
Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2016-06, Vol.61, p.82-96
Main Authors: Han, Mingda, Evsikov, Alexei V., Zhang, Lifeng, Lastra-Vicente, Rosana, Linask, Kersti K.
Format: Article
Language:English
Subjects:
Acyl-CoA Dehydrogenase - genetics
Animals
Cadherins - metabolism
Cardiotonic Agents - pharmacology
Computational Biology
Embryo, Mammalian
Fatty acid oxidation
Female
Folic acid
Folic Acid - pharmacology
Gender
Heart
Heart - drug effects
Heart - embryology
Homocysteine
Homocysteine - toxicity
Lipid Metabolism - drug effects
Lithium
Lithium Chloride - toxicity
Male
Mice, Inbred C57BL
Mouse embryo
Myocardium - metabolism
Placenta
Placenta - drug effects
Placenta - metabolism
Placentation - drug effects
Pregnancy
Transcriptome
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Summary:•We demonstrate embryonic cell processes that are altered by homocysteine and lithium.•Bioinformatics analysis show processes primarily changed relate to lipid metabolism.•The lipid metabolic changes are dependent on the gender of the embryo.•The transcriptome of male embryos are more altered than of the female with exposure.•Changes with exposures can be prevented by high dose folate dietary supplementation. Embryonic exposures can increase the risk of congenital cardiac birth defects and adult disease. The present study identifies the predominant pathways modulated by an acute embryonic mouse exposure during gastrulation to lithium or homocysteine that induces cardiac defects. High dose periconceptional folate supplementation normalized development. Microarray bioinformatic analysis of gene expression demonstrated that primarily lipid metabolism is altered after the acute exposures. The lipid-related modulation demonstrated a gender bias with male embryos showing greater number of lipid-related Gene Ontology biological processes altered than in female embryos. RT-PCR analysis demonstrated significant change of the fatty acid oxidation gene Acadm with homocysteine exposure primarily in male embryos than in female. The perturbations resulting from the exposures resulted in growth-restricted placentas with disorganized cellular lipid droplet distribution indicating lipids have a critical role in cardiac-placental abnormal development. High folate supplementation protected normal heart-placental function, gene expression and lipid localization.
ISSN:0890-6238
1873-1708
DOI:10.1016/j.reprotox.2016.03.039