title: Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation.
abstract: 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.
authors.affiliation: Dept. of Pediatrics, USF Morsani College of Medicine, USF Children's Research Institute, St. Petersburg, FL33701, United States.
authors.forename: Mingda
authors.initials: M
authors.lastname: Han
authors.affiliation: Dept of Molecular Medicine, USF Morsani College of Medicine, Tampa, FL, United States.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Evsikov
authors.affiliation: Dept. of Pediatrics, USF Morsani College of Medicine, USF Children's Research Institute, St. Petersburg, FL33701, United States.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Dept. of Pediatrics, USF Morsani College of Medicine, USF Children's Research Institute, St. Petersburg, FL33701, United States.
authors.forename: Rosana
authors.initials: R
authors.lastname: Lastra-Vicente
authors.affiliation: Dept. of Pediatrics, USF Morsani College of Medicine, USF Children's Research Institute, St. Petersburg, FL33701, United States. Electronic address: klinask@health.usf.edu.
authors.forename: Kersti K
authors.initials: KK
authors.lastname: Linask
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000235:genetics; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019295:Computational Biology; D004622:Embryo, Mammalian; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006710:Homocysteine / Q000633:toxicity*; D050356:Lipid Metabolism / Q000187:drug effects*; D018021:Lithium Chloride / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D010929:Placentation / Q000187:drug effects*; D011247:Pregnancy; D059467:Transcriptome
chemical_list: D015820:Cadherins; D002316:Cardiotonic Agents; D006710:Homocysteine; C070896:M-cadherin; D005492:Folic Acid; D042964:Acyl-CoA Dehydrogenase; D018021:Lithium Chloride
keywords: Fatty acid oxidation; Folic acid; Gender; Heart; Homocysteine; Lithium; Mouse embryo; Placenta