Glyphosate-Based Herbicide Stress During Pregnancy Impairs Intestinal Development in Newborn Piglets by Modifying DNA Methylation

Glyphosate-based herbicide (GBH), a feed contaminant,
has been
proven to impair the growth and development of humans and animals.
Previous research has revealed that maternal toxin exposure during
pregnancy could cause permanent fetal changes by epigenetic modulation.
However, there was insufficient evidence of the involvement of DNA
methylation in maternal GBH exposure-induced intestinal health of
offspring. Here, we established pregnant sow exposure models to investigate
the effects of GBH on the intestinal DNA methylation of newborn piglets.
The results showed gestational exposure to GBH compromises the intestinal
function of newborn piglets as well as decreases the mRNA expression
of Dnmt1 and Dnmt3b jejunum. Further RRBS DNA methylation analysis
revealed genomic hypomethylation in jejunum, and the differentially
methylated regions were enriched in the pathways of intestinal development
and food digestion and the related GO terms. Additionally, integrative
analysis of methylome and transcriptome identified 23 genes showing
inverse correlations and indicated the underlying injury mechanisms
upon maternal GBH. These findings provide new insights and fundamental
knowledge into the possible involvement of DNA methylation in the
intestinal injury of offspring induced by maternal GBH exposure during
pregnancy, which drives manufacturers to develop low-toxicity herbicide
to ensure food safety and human health.