Endosulfan affects uterine development and functional differentiation by disrupting Wnt7a and β-catenin expression in rats

Mol Cell Endocrinol. 2016 Apr 15:425:37-47. doi: 10.1016/j.mce.2016.02.011. Epub 2016 Feb 18.

Abstract

Neonatal exposure to a low dose of endosulfan may disrupt the expression of Wnt7a and β-catenin during uterine development leading to the failure of uterine functional differentiation during implantation. New-born female Wistar rats were treated with vehicle, endosulfan (600 μg/kg/d, E600) or diethylstilbestrol (0.2 μg/kg/d, DES) on postnatal days (PNDs) 1, 3, 5 and 7. Subsequently, uterine histomorphology and the protein expression of Wnt7a and β-catenin were evaluated on PND8, PND21 and gestational day (GD) 5 (pre-implantation period). In the E600 rats, Wnt7a and β-catenin protein expression was increased in the epithelium on PND8, and Wnt7a expression was decreased in the endometrial glands on PND21. On GD5, the number of uterine glands was decreased in the E600-and DES-treated rats. In addition, Wnt7a expression was decreased in all uterine compartments, and β-catenin expression was increased in the luminal and glandular epithelia of the E600-and DES-treated rats. Disruption of Wnt7a and β-catenin uterine expression in the prepubertal and adult females altered the uterine preparation for embryo implantation, which could be associated with the subfertility triggered by endosulfan.

Keywords: Endosulfan; Implantation; Uterus; Wnt7a; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation / drug effects
  • Diethylstilbestrol / toxicity
  • Endosulfan / administration & dosage
  • Endosulfan / adverse effects*
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Uterus / drug effects*
  • Uterus / growth & development
  • Uterus / metabolism
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Wnt7a protein, rat
  • beta Catenin
  • Diethylstilbestrol
  • Endosulfan