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HERO ID
6410167
Reference Type
Journal Article
Title
Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome
Author(s)
Dolinoy, DC; Weidman, JR; Waterland, RA; Jirtle, RL
Year
2006
Is Peer Reviewed?
Yes
Journal
Environmental Health Perspectives
ISSN:
0091-6765
EISSN:
1552-9924
Volume
114
Issue
4
Page Numbers
567-572
Language
English
PMID
16581547
DOI
10.1289/ehp.8700
Abstract
Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States. Here, we report that maternal dietary genistein supplementation of mice during gestation, at levels comparable with humans consuming high-soy diets, shifted the coat color of heterozygous viable yellow agouti (A(vy/a) offspring toward pseudoagouti. This marked phenotypic change was significantly associated with increased methylation of six cytosine-guanine sites in a retrotransposon upstream of the transcription start site of the Agouti gene. The extent of this DNA methylation was similar in endodermal, mesodermal, and ectodermal tissues, indicating that genistein acts during early embryonic development. Moreover, this genistein-induced hypermethylation persisted into adulthood, decreasing ectopic Agouti expression and protecting offspring from obesity. Thus, we provide the first evidence that in utero dietary genistein affects gene expression and alters susceptibility to obesity in adulthood by permanently altering the epigenome.
Keywords
; Agouti Signaling Protein; Animals; Base Sequence; Body Weight; Chromatography; High Pressure Liquid; DNA Methylation; DNA Primers; Female; Fetus; Genistein/pharmacology; Hair Color/drug effects; Intercellular Signaling Peptides and Proteins/genetics; Maternal Exposure; Mice; Obesity/prevention & control; Pregnancy; Index Medicus/
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