Potential involvement of placental AhR in unexplained recurrent spontaneous abortion

Reprod Toxicol. 2016 Jan:59:45-52. doi: 10.1016/j.reprotox.2015.11.005. Epub 2015 Nov 22.

Abstract

Recurrent spontaneous abortion (RSA) is a common complication of pregnancy. Recent studies have demonstrated that the aryl hydrocarbon receptor (AhR) might play important roles in establishing and maintaining early pregnancy. In this study, we found that placental AhR protein levels were significantly lower and placental CYP1A1 mRNA levels were higher in unexplained RSA (URSA) patients than in control subjects. The results of immunohistochemical analyzes showed that placental AhR was expressed in syncytiotrophoblast cells and that the level of AhR was markedly lower in these cells in URSA subjects than in control subjects. β-Naphthoflavone (β-NF, an AhR ligand) at 5μM significantly inhibited proliferation and migration in HTR-8/SVneo cells and was associated with the activation of AhR. Moreover, overexpressing AhR in JAR cells significantly increased CYP1A1 mRNA levels and inhibited cell migration. These results indicate that AhR is highly activated in URSA placentas and that the activation of AhR in the placenta might impair trophoblast cell proliferation and migration, possibly leading to the occurrence of URSA.

Keywords: Aryl hydrocarbon receptor; Migration; Placenta; Proliferation; Trophoblast cells; Unexplained recurrent spontaneous abortion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / diagnosis
  • Abortion, Habitual / etiology
  • Abortion, Habitual / metabolism*
  • Adult
  • Basic Helix-Loop-Helix Transcription Factors / agonists
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunohistochemistry
  • Indoles / pharmacology
  • Placenta / drug effects
  • Placenta / metabolism*
  • Pregnancy
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Thiazoles / pharmacology
  • Time Factors
  • Transfection
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism
  • beta-Naphthoflavone / pharmacology

Substances

  • 2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Indoles
  • Receptors, Aryl Hydrocarbon
  • Thiazoles
  • beta-Naphthoflavone
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1