Maternal Diet during Pregnancy Induces Gene Expression and DNA Methylation Changes in Fetal Tissues in Sheep

Abstract

Studies in rats and mice have established that maternal nutrition induces epigenetic modifications, sometimes permanently, that alter gene expression in the fetus, which in turn leads to phenotypic changes. However, limited data is available on the influence of maternal diet on epigenetic modifications and gene expression in sheep. Therefore, the objectives of this study were to investigate the impact of different maternal dietary energy sources on the expression of imprinted genes in fetuses in sheep. Ewes were naturally bred to a single sire and from days 67 ± 3 of gestation until necropsy (days 130 ± 1), they were fed one of three diets of alfalfa haylage (HY; fiber), corn (CN; starch), or dried corn distiller’s grains (DG; fiber plus protein plus fat). A total of 26 fetuses were removed from the dams and longissimus dorsi, semitendinosus, perirenal adipose depot, and subcutaneous adipose depot tissues were collected for expression and DNA methylation analyses. Expression analysis of nine imprinted genes and three DNA methyltransferase (DNMTs) genes showed significant effects of the different maternal diets on the expression of these genes. The methylation levels of CpG islands of both IGF2R and H19 were higher in HY and DG than CN fetuses in both males and females. This result is consistent with the low amino acid content of the CN diet, a source of methyl group donors, compared to HY and DG diets. Thus, results of this study provide evidence of association between maternal nutrition during pregnancy and transcriptomic and epigenomic alterations of imprinted genes and DNMTs in the fetal tissues.

Effects of maternal nutrition on the expression of genomic imprinted genes in ovine fetuses

“…Interestingly, we found most of the disturbed gene expression were located in the KCNQ1 and IGF2/H19 clusters, consistent with the role of IGF2 as a major fetal growth regulator [54]. Diets of pregnant ewes containing different starch/fiber/protein portions have been shown to change the CpG methylation levels of specific imprinted genes such as IGF2R and H19 [20]. Our data also showed that despite the dramatic maternal diet changes, the allelic expression pattern was not affected, further suggesting that gene expression levels and imprinted patterns may be regulated through different epigenetic mechanisms.…”

“…Poor maternal nutrition, either over- or restricted-feeding during pregnancy [19], has been shown to cause abnormal DNA methylation and expression of a few imprinted genes, such as IGF2R and H19 in ovine fetuses [20]. NGS, however, has the power to simultaneously determine expression changes of all known imprinted genes, which has yet to be conducted in sheep.…”

Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation

“…DNMT1 produces the enzyme DNA methyltransferase, which maintains DNA methylation in newly synthesized DNA strands. 5 Animal studies [20][21][22] have shown that maternal diet can influence DNMT1 methylation/expression. For example, a choline deficiency in pregnant rats (hypo)methylates the regulatory CpGs within the DNMT1 gene, leading to its overexpression; this results in an increase of global and gene specific (IGF2) DNA methylation.…”

The Omics of Obesity

“…These amino acids included levels of alanine, glycine, glutamate, tryptophan and tyrosine [30]. In a metabolomic profiling study of 74 obese and 67 lean individuals, a number of differences in fatty and amino acids were reported [31]. Levels of free fatty acids C14:0, C16:0, C16:1, C18:1, C20:4 remained elevated in obese as compared to lean subjects.…”

“…Therefore, epigenetic modifications are hypothesised to be trans-generational and have been shown to be reversible whereby specific epigenetic marks can be turned on or off depending on the stimuli (Bishop et al). Most of these studies have been performed in animal models including mice [24,25], rats [26,27], Macaque [28], drosophila [29] and sheep [23,30,31]. The effects of the in utero environment on foetal programming in humans have not been well explored.…”