Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction

Toxicol Sci. 2017 Nov 1;160(1):150-160. doi: 10.1093/toxsci/kfx166.


Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is associated with hypothyroxinemia and decreases in placental glucose transporter expression and activity. The objective of this study was to investigate the influence of TCS on glucose homeostasis and insulin sensitivity in gestational mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to GD17 significantly increased their levels of fasting plasma glucose and serum insulin, and insulin content in pancreatic β-cells with reduced homeostasis model assessment (HOMA)-β index and increased HOMA-IR index. Area under curve (AUC) of glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice showed a significant decrease in the levels of thyroxine and triiodothyroninelevels, PPARγ and glucose transporter 4 (GLUT4) expression, and Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the levels of insulin, PPARγ and GLUT4 expression, and Akt phosphorylation. Activation of PPARγ by administration of rosiglitazone recovered the decrease in Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) in Ng-mice reduced thyroid hormones levels, it did not cause the insulin resistance or affect PPARγ and GLUT4 expression, and Akt phosphorylation. The findings indicate that the exposure of gestational mice to TCS (≥8 mg/kg) results in insulin resistance via thyroid hormones reduction.

Keywords: Triclosan; gestational diabetes mellitus; insulin resistance; thyroid hormones.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Anti-Infective Agents, Local / toxicity*
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / chemically induced*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Female
  • Gestational Age
  • Glucose Transporter Type 4 / metabolism
  • Insulin / blood
  • Insulin Resistance*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Male
  • Maternal Exposure / adverse effects
  • Mice, Inbred ICR
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • PPAR gamma / metabolism
  • Phosphorylation
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroxine / blood*
  • Time Factors
  • Triclosan / toxicity*
  • Triiodothyronine / blood


  • Anti-Infective Agents, Local
  • Biomarkers
  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • PPAR gamma
  • Slc2a4 protein, mouse
  • Triiodothyronine
  • Triclosan
  • Proto-Oncogene Proteins c-akt
  • Thyroxine