Maternal Genistein Alters Coat Color and Protects Avy Mouse Offspring from Obesity by Modifying the Fetal Epigenome

By Dana C. Dolinoy, J. Weidman, Robert A. Waterland, R. Jirtle. Environmental Health Perspectives, 2006

973 citations recorded by the source corpus.

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 (Avy/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.

Subfields: Molecular Biology, Pathology and Forensic Medicine, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/4a0104cf12b6ab9af786efe6ff59f8812e87618f

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Citations in the corpus

Prenatal environmental exposures, epigenetics, and disease (2011, positive): “The fact that CpG sites were altered in tissues derived from the ectodermal, endodermal, and mesodermal lineages indicates that methylation profiles were changed early in embryonic development [7,18,37].”
Endocrine Disrupting Chemicals and Disease Susceptibility (2011, background): “Many other chemicals have also been implicated in promoting toxicity for multiple generations, including BPA [66, 67], polycyclic hydrocarbons [68, 69], cocaine [69], pesticides [70], and phytoestrogens [71-73].”
Epigenetics and the environment: emerging patterns and implications (2012, background): “Also, the addition of genistein — a phyto-oestrogenic component of soy beans — to the maternal diet, led to increased DNA methylation at the locus in the offsprin”
Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. (2007, background): “There also is growing evidence for transplacental cancer chemopreventive effects of I3C and other dietary modulators, involving changes in DNA promoter methylation, chromatin remodeling, and expression of imprinted genes [117–120].”
Epigenetic mechanisms that underpin metabolic and cardiovascular diseases (2009, background): “By contrast, maternal feeding of the soy isoflavone genistein leads to promoter hypermethylation, decreased prevalence of obesity and brown coat color in the offspring”
Child health, developmental plasticity, and epigenetic programming. (2011, background): “Jirtle and colleagues (530) reported 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 (Avy/a) offspring toward pseudo-agouti.”