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 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 granulopoiesis, 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 hematopoiesis 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.

Estrogen Defines the Dorsal-Ventral Limit of VEGF Regulation to Specify the Location of the Hemogenic Endothelial Niche

“…The fact that XEs could affect the HSC niche raises important questions about the long-term deleterious effects of in utero exposure on hematopoietic development and homeostasis. While not specifically examined here, pregnant mice fed a diet rich in genistein had pups with increased erythropoiesis and granulopoiesis at 12 weeks of age (Vanhees et al, 2011). Genistein can also induce rearrangements in the Mixed Lineage Leukemia (MLL) gene in human CD34+ cells resembling those commonly seen in infant leukemias (Barjesteh van Waalwijk van Doorn-Khosrovani et al, 2007) and epidemiological studies show exposure to dietary flavonoids during pregnancy is linked to infant leukemia development (Ross, 2000).…”

Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention

“…Genistein has been found to be capable of modulating important epigenetic events, such as DNA methylation and histone tail modifications [77–79]. The inhibitory effect on DNMTs and histone modifying activities of genistein has been established in many similar reports [80–82]. Reactivation of the tumor suppressor genes p21 CIP1/WAF1 , RAR β and MGMT and p16 INK4a through promoter hypomethylation and active chromatin modifications after genistein treatment in breast cancer, squamous cell carcinoma and prostate cancer cells led to cell cycle arrest and cell death [77, 79].…”

γ-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+dendritic cells in utero and allergic inflammation in neonates

“…Interestingly, there are functional changes in the DCs from offspring of allergic mothers (26). Maternal exposure to environmental factors, including high-fat diets, can alter neonatal hematopoietic or metabolic function (15,27,41,51,61,66,83,93). In our studies, maternal supplementation with D-␥-tocopherol increased development of CD11c ϩ CD11b ϩ DCs in the fetus and in neonates.…”