Exposure to Aroclor 1254 differentially affects the survival of pancreatic β-cells and α-cells in the male mice and the potential reason

Ecotoxicol Environ Saf. 2020 Jan 30;188:109875. doi: 10.1016/j.ecoenv.2019.109875. Epub 2019 Nov 6.

Abstract

Previous works showed that chronic exposure to Aroclor 1254 disrupted glucose homeostasis and induced insulin resistance in male mice. To further observe the different effects of Aroclor 1254 exposure on the pancreatic α-cells and β-cells, male mice were exposed to Aroclor 1254 (0, 0.5, 5, 50, 500 μg/kg) for 60 days, the pancreas was performed a histological examination. The results showed that the percentage of apoptosis cell (indicated by TUNEL assay) was increased in both α-cells and β-cells, as the Aroclor 1254 dose was increased; the proliferation (indicated by PCNA expression) rate of β-cells was elevated while that of α-cells was not affected, resulting in an increased β-cell mass and a decreased α-cell mass in a dose-depend manner. The number of Pdx-1 positive β-cells was significantly increased whereas that of Arx positive α-cells was markedly decreased, indicating an enhanced β-cell neogenesis and a weakened α-cell neogenesis. The drastically reduction of serum testosterone levels in all the treatments suggested an anti-androgenic potency of Aroclor 1254. The up-regulation of estrogen receptors (ERα and ERβ) and androgen receptor in β-cells might be responsible for the increased β-cell mass and neogenesis.

Keywords: Apoptosis; Arx; Pdx-1; Polychlorinated biphenyls; Proliferation; α-Cell; β-Cell.

MeSH terms

  • Animals
  • Antithyroid Agents / toxicity*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Chlorodiphenyl (54% Chlorine) / toxicity*
  • Glucagon-Secreting Cells / drug effects*
  • Glucagon-Secreting Cells / metabolism
  • Glucagon-Secreting Cells / pathology
  • Homeodomain Proteins / metabolism
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Mice
  • Receptors, Androgen / metabolism
  • Receptors, Estrogen / metabolism
  • Testosterone / blood
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism

Substances

  • ARX protein, mouse
  • Antithyroid Agents
  • Homeodomain Proteins
  • Receptors, Androgen
  • Receptors, Estrogen
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein
  • Chlorodiphenyl (54% Chlorine)
  • Testosterone