Neonatal exposure to a glyphosate-based herbicide alters uterine decidualization in rats

Reprod Toxicol. 2017 Oct:73:87-95. doi: 10.1016/j.reprotox.2017.07.022. Epub 2017 Aug 2.

Abstract

We investigated whether defective modulation of uterine signaling may cause decidualization failure in rats neonatally exposed to a glyphosate-based herbicide (GBH). Female pups received vehicle or 2mg/kg of GBH from postnatal day (PND) 1 to PND7. On PND8 and PND21, Wnt5a and β-catenin expression was evaluated in uterine samples. On gestational day (GD) 9, Wnt5a, Wnt7a and β-catenin expression and Dkk1 and sFRP4 mRNA were evaluated on implantation sites. On PND8, GBH-exposed rats showed increased Wnt5a and β-catenin expression in luminal epithelium (LE), whereas on PND21, they showed increased Wnt5a and β-catenin expression in subepithelial stroma but decreased β-catenin expression in glandular epithelium. On GD9, GBH-exposed rats showed decreased Wnt5a and Wnt7a expression in the antimesometrial zone and LE respectively, without changes in β-catenin expression, while Dkk1 and sFRP4 were up- and down-regulated respectively. We concluded that neonatal GBH exposure may lead to embryo losses by disturbing uterine signaling.

Keywords: Decidualization; Dkk1; Glyphosate-based herbicide; Implantation sites; Wnt5a; Wnt7a; sFRP4; β-catenin.

MeSH terms

  • Animals
  • Female
  • Glycine / analogs & derivatives*
  • Glycine / toxicity
  • Glyphosate
  • Herbicides / toxicity*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Maternal-Fetal Exchange
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Rats, Wistar
  • Ribosomal Proteins / genetics
  • Signal Transduction / drug effects
  • Uterus / drug effects*
  • Uterus / metabolism
  • Wnt Proteins / metabolism
  • Wnt-5a Protein / metabolism
  • beta Catenin / metabolism

Substances

  • Ctnnb1 protein, rat
  • Dkk1 protein, rat
  • Herbicides
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • Ribosomal Proteins
  • Sfrp4 protein, rat
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, rat
  • Wnt7a protein, rat
  • beta Catenin
  • Rpl19 protein, rat
  • Glycine