title: Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood.
abstract: The flavonoid quercetin is a powerful iron chelator, capable of oxidizing heme iron in hemoglobin from Fe(2+) to Fe(3+). Moreover, quercetin crosses the placenta and accumulates in the fetus. Since adaptations made by the fetus to cope with inappropriate nutrition may lead to permanent changes, a relative high intake of quercetin may have detrimental affects later in life. Therefore, we investigated the effects of maternal exposure to quercetin (302 mg/kg feed), starting from 3 days before conception until the end of gestation, on erythropoiesis and iron homeostasis at embryonic day 14.5 and in 12-week old mice. During fetal development, quercetin exposure had no effect on the erythroid lineage switch and concomitant globin switch. However, adult mice prenatally exposed to quercetin had significant increase iron storage in the liver, by upregulating iron-associated cytokine expression (hepcidin, IL-1β, IL-6 and IL-10). These long term changes in gene expression could be mediated through epigenetic modifications, as prenatal quercetin exposure resulted in a modest hypermethylation of repetitive elements. Despite the increased iron levels, oxidative stress was significantly decreased in the liver of these animals as assessed by 8-oxo-dG levels. These data suggest that prenatal quercetin exposure results in increased iron storage, while decreasing oxidative stress induced DNA damage together with a shift towards increased expression of inflammation associated cytokines in the liver at adult age.
authors: Department of Toxicology, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht MUMC+, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors: Kimberly
authors: K
authors: Vanhees
authors: Roger W
authors: RW
authors: Godschalk
authors: Anneke
authors: A
authors: Sanders
authors: Sahar Barjesteh
authors: SB
authors: van Waalwijk van Doorn-Khosrovani
authors: Frederik J
authors: FJ
authors: van Schooten
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011794:Quercetin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D007502:Iron Chelating Agents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D011794:Quercetin; D007501:Iron; D003849:Deoxyguanosine