mRNA expression of Hoxa10 gene and epigenetic marks on its regulatory regions in the uterus of non-exposed and glyphosate or a glyphosate-based herbicide exposed Wistar rats

Abstract

In this work, we investigated the effect of perinatal exposure to a glyphosate-based herbicide (GBH) or glyphosate (Gly), the active ingredient, on the transcriptional regulation of Hoxa10 gene and epigenetic marks such as DNA methylation status and histone post-translational modifications (hPTMs) on Hoxa10 regulatory regions (RRs) and major epigenetic enzymes during the receptive stage in Wistar rats. GBH and Gly down-regulated Hoxa10 mRNA. GBH and Gly increased DNA methylation levels and Gly also induced higher levels than GBH in all the RRs analyzed. Both GBH and Gly enriched histone 3 (H3) and H4 acetylation in most of the RRs. While GBH caused higher H3 acetylation, Gly caused higher H4 acetylation in all RRs. Finally, GBH and Gly enhanced histone H3 lysine 27 trimethylation (H3K27me3) marker at 3 out of 4 RRs studied which was correlated with increased levels of the histone methyltransferase EZH2. In conclusion, exposure to GBH or Gly during perinatal period induces epigenetic modifications in RRs of uterine Hoxa10 gene.