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Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.

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.

SUBMITTER: Dolinoy DC

PROVIDER: S-EPMC1440782 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.

Dolinoy Dana C DC Weidman Jennifer R JR Waterland Robert A RA Jirtle Randy L RL

Environmental health perspectives 20060401 4

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 d ...[more]

PMID: 16581547

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Project description:Recent research revealed that dietary genistein supplementation for breeder hens can improve the immune function of offspring chicks. However, it remains unknown whether this maternal effect could improve the intestinal health of offspring. This study was conducted to explore the mechanism involved in the maternal effect of genistein on the intestinal mucosa and microbial homeostasis of chicken offspring. A total of 120 Qiling breeder hens were fed a basal diet, a 20 mg/kg genistein-supplemented diet, or a 40 mg/kg genistein-supplemented diet for 4 weeks before collecting their eggs. After hatching, 180 male offspring (60 chickens from each group) were randomly selected and divided into three groups: (1) the offspring of hens fed a basal diet (CON); (2) the offspring of hens fed a low-dose genistein-supplemented diet (LGE); (3) the offspring of hens fed a high-dose genistein-supplemented diet (HGE). At 17 d, 72 male offspring (48 chickens from CON and 24 chickens from LGE) were divided into three groups: (1) the offspring of hens fed a basal diet (CON); (2) the CON group challenged with LPS (LPS); (3) the LGE group challenged with LPS (LPS + LGE). The results showed that maternal genistein supplementation increased the birth weight and serum level of total protein (TP), followed by improved intestinal villus morphology. Continuously, the maternal effect on the body weight of chicks lasted until 21 d. Additionally, it was observed that maternal genistein supplementation exhibited protective effects against LPS-induced morphological damage and intestinal mucosal barrier dysfunction by upregulating the expression of tight junction proteins, specifically ZO-1, Claudin1, E-cadherin, and Occludin, at 21 d. Using 16S rRNA gene sequencing, we demonstrated that maternal supplementation of genistein has the potential to facilitate the maturation of newly hatched chicken offspring by enhancing the abundance of Escherichia coli. Additionally, maternal genistein supplementation can effectively reduce the abundance of Gammaproteobacteria, thus mitigating the risk of bacterial diversity impairment of LPS. In light of these findings, maternal genistein supplementation holds promise as a potential strategy for ameliorating intestinal mucosal damage and modulating the microbiome in chicken offspring.

Dataset Information

Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.

Publications

Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.

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