Effects of parental folate deficiency on the folate content, global DNA methylation, and expressions of FRα, IGF-2 and IGF-1R in the postnatal rat liver

Abstract

We examined the effect of parental folate deficiency on the folate content, global DNA methylation, folate receptor-alpha (FRα), insulin-like-growth factor-2 (IGF-2) and -1 receptor (IGF-1R) in the liver and plasma homocysteine in the postnatal rat. Male and female rats were randomly fed a folic acid-deficient (paternal folate-deficient, PD and maternal folate-deficient, MD), or folic acid-supplemented diet (paternal folate-supplemented, PS and maternal-folate-supplemented, MS) for four weeks. They were mated and grouped accordingly: PSxMS, PSxMD, PDxMS, and PDxMD. Pups were killed on day 21 of lactation. The hepatic folate content was markedly reduced in the PDxMD and PSxMD and PDxMS as compared with the PSxMS group. The hepatic global DNA methylation was decreased in the PDxMS and PSxMD groups as much as in the PDxMD group, and all the three groups were significantly lower as compared to the PSxMS group. There were no significant differences in the hepatic FRα, IGF-2 and IGF-1R expressions among the groups. Positive correlations were found between the hepatic folate content and global DNA methylation and protein expressions of FRα, IGF-2 and IGF-1R, whereas an inverse correlation was found between hepatic folate content and plasma homocysteine level in the 3-week-old rat pup. The results of this study show that both paternal and maternal folate deficiency at mating can influence the folate content and global DNA methylation in the postnatal rat liver.

Methyl donors dietary supplementation to gestating sows diet improves the growth rate of offspring and is associating with changes in expression and DNA methylation of insulin‐like growth factor‐1 gene

“…On the contrary, Henderson, Aleliunas, Tai, Green, and Devlin () found that serum IGF‐1 concentrations were decreased in the offspring born to VB 12 ‐deficiency dams, whereas maternal dietary VB 12 supplementation returned the offspring serum IGF‐1 to normal. Similar, the expressions of hepatic IGF‐1 mRNA and protein were increased in the MD compared with CON offspring, further indicated that maternal MD supplement induced greater hepatic IGF‐1 expression and resulted in elevated circulating IGF‐1, which agrees with the results in rat that serum IGF‐1 concentrations and hepatic IGF‐1 mRNA abundance were upregulated in the offspring born to folate‐sufficiency dams (Mejos, Kim, Lim, & Chang, ). Therefore, the increases of hepatic IGF‐1 expression and serum IGF‐1 were the contributing factor to improve the growth performance of offspring with maternal MD supplementation.…”

“…The age of the offspring reaches to 110 kg: CON = 196.2 days; MD = 192.2 days. *p < 0.05, significantly different from CON (Mejos, Kim, Lim, & Chang, 2013). Therefore, the increases of hepatic IGF-1 expression and serum IGF-1 were the contributing factor to improve the growth performance of offspring with maternal MD supplementation.…”

The effect of paternal dietary folic acid on male fertility and embryo development in Balb/c mice

“…Additionally, folate deficiency has been associated with global DNA hypomethylation [11]. DNA methylation is critical in the regulation of gene expression and in the maintenance of genome stability.…”

“…Impaired nucleotide synthesis can also cause increased mutation rates, as well as genome instability, including DNA double strand breaks and chromosome damage. Additionally, folate deficiency has been associated with aberrant DNA methylation because methionine is used to synthesize AdoMet, the major cellular methyl donor [11].…”

“…Unfortunately, a large proportion of women do not take a FA-containing supplement as recommended. As such, Canada made the fortification of white flour with FA mandatory in 1998 [11]. Mandatory FA fortification has reduced the prevalence of folate deficiency to less than 1% in the general population and importantly, reduced the incidence of NTDs by 45% [12,13].…”