title: Oxidized frying oil and its polar fraction fed to pregnant mice are teratogenic and alter mRNA expressions of vitamin A metabolism genes in the liver of dams and their fetuses.
abstract: We previously observed a higher incidence of congenital malformations in the fetuses of dams fed an oxidized frying oil (OFO)-containing diet during pregnancy. In this study, we hypothesized that, during pregnancy, maternal ingestion of OFO, specifically the oxidized components (i.e. the polar fraction), modulates peroxisome proliferator-activated receptor (PPARα) or aryl hydrocarbon receptor (AhR) transactivity, altering the metabolism of retinoic acid (RA), a well-characterized morphogen, resulting in teratogenesis. Pregnant C57BL/6J mice were divided into four groups which, from d1 (conception) to d18, were fed a diet containing 10 g/100 g of fresh soybean oil (SO), OFO or the non-polar (NP) or polar (PO) fraction of OFO. Reporter assays testing the transactivity of PPARα and AhR showed that free fatty acids from OFO, specifically the PO fraction, up-regulated PPARα transactivity and down-regulated AhR transactivity. In vivo study showed that the PO fraction group had a significantly higher number of dead fetuses and resorptions per litter than the SO and NP fraction groups. The incidence of abnormalities in terms of gross morphology and skeletal ossification of the fetus was greatest in the PO fraction group, followed by the OFO group, both values being significantly higher than in the other two groups. Hepatic expression of genes encoding enzymes associated with RA synthesis and catabolism in dams and fetuses was differentially affected by PO fraction assault. We conclude that OFO-mediated teratogenesis is associated with disturbed RA metabolism in the dams and fetuses caused, at least in part, by modulation of PPARα and AhR transactivity by the oxidized components in OFO.
authors.affiliation: Institute of Nutrition, China Medical University, Taichung 404, Taiwan.
authors.forename: Chin-Fang
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Institute of Nutrition, China Medical University, Taichung 404, Taiwan.
authors.forename: Yu-Shun
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Institute of Nutrition, China Medical University, Taichung 404, Taiwan.
authors.forename: Zong-Cian
authors.initials: ZC
authors.lastname: Chiang
authors.affiliation: Department of Applied Toxicology, Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Taichung 413, Taiwan.
authors.forename: Shui-Yuan
authors.initials: SY
authors.lastname: Lu
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan.
authors.forename: Sunny Li-Yun
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Institute of Nutrition, China Medical University, Taichung 404, Taiwan. Electronic address: pmchao@mail.cmu.edu.tw.
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Chao
mesh_terms: D000818:Animals; D003296:Cooking / Q000379:methods*; D004042:Dietary Fats, Unsaturated / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism*
chemical_list: D004042:Dietary Fats, Unsaturated; D047493:PPAR alpha; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; D014801:Vitamin A
keywords: Aryl hydrocarbon receptor; Gestation; Oxidized frying oil; PPARα; Retinoic acid; Teratogenesis