|Waterland, Robert - Rob|
Submitted to: Environmental Health Perspectives
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/26/2006
Publication Date: 4/20/2006
Citation: Dolinoy, D.C., Weidman, J.R., Waterland, R.A., Jirtle, R.L. 2006. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environmental Health Perspectives. 114(4):567-572. Interpretive Summary: Genistein is a bioactive component of soy products. There is concern that female consumption of soy before and during pregnancy may affect developmental processes in her fetus. To test this, we supplemented special mice (agouti viable yellow) with genistein before and during pregnancy. Agouti viable yellow mice are sensitive to components of the mother’s diet; their coat color actually changes if maternal diet affects development, a process known as epigenetics. Genistein supplementation changed the coat color of the agouti viable yellow offspring. Hence, female genistein consumption before and during pregnancy in humans may affect developmental processes and have consequences for later health of her offspring.
Technical 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 (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.