Epigenetics: prenatal exposure to genistein leaves a permanent signature on the hematopoietic lineage

ABSTRACT Recent studies demonstrate that maternal diet during pregnancy results in long‐lasting effects on the progeny. Supplementation of maternal diet with genistein, a phytoestrogen ubiquitous in the daily diet, altered coat color of agouti mice due to epigenetic changes. We studied hematopoiesis...

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Published in:The FASEB journal 2011-02, Vol.25 (2), p.797-807
Main Authors: Vanhees, Kimberly, Coort, Susan, Ruijters, Erik J. B., Godschalk, Roger W. L., Schooten, Frederik J., Doorn‐Khosrovani, Sahar Barjesteh van Waalwijk
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells - drug effects
DNA Methylation
Epigenomics
Erythropoiesis - drug effects
Female
flavonoid
gene expression
Gene Expression Regulation - drug effects
Genistein - toxicity
hematopoiesis
in utero exposure
Liver - metabolism
Male
Mice
Phytoestrogens - toxicity
Pregnancy
Prenatal Exposure Delayed Effects
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Summary:ABSTRACT Recent studies demonstrate that maternal diet during pregnancy results in long‐lasting effects on the progeny. Supplementation of maternal diet with genistein, a phytoestrogen ubiquitous in the daily diet, altered coat color of agouti mice due to epigenetic changes. We studied hematopoiesis of mice prenatally exposed to genistein (270 mg/kg feed) compared with that of mice prenatally exposed to phytoestrogen‐poor feed and observed a significant increase in granulopoi‐esis, erythropoiesis, and mild macrocytosis at the adult age of 12 wk. Genistein exposure was associated with hypermethylation of certain repetitive elements, which coincided with a significant down‐regulation of estrogen‐responsive genes and genes involved in hematopoi‐esis in bone marrow cells of genistein‐exposed mice, as assessed by microarray technology. Although genistein exposure did not affect global methylation in fetal liver of fetuses at embryonic day 14.5, it accelerated the switch from primitive to definitive erythroid lineage. Taken together, our data demonstrate that prenatal exposure to genistein affects fetal erythropoiesis and exerts lifelong alterations in gene expression and DNA methylation of hematopoietic cells.—Vanhees, K., Coort, S., Ruitjers, E.J. B., Godschalk, R. W. L., van Schooten, F. J., Barjesteh van Waalwijk van Doorn‐Khosrovani, S. Epigenetics: prenatal exposure to genistein leaves a permanent signature on the hematopoietic lineage. FASEB J. 25, 797–807 (2011). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.10-172155