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.