Effects of hypo- and hyperthyroidism on proliferation, angiogenesis, apoptosis and expression of COX-2 in the corpus luteum of female rats

Reprod Domest Anim. 2013 Aug;48(4):691-8. doi: 10.1111/rda.12149. Epub 2013 Jan 31.

Abstract

Although thyroid dysfunction occurs frequently in humans and some animal species, the mechanisms by which hypo- and hyperthyroidism affect the corpus luteum have not been thoroughly elucidated. This study evaluated the levels of proliferative activity, angiogenesis, apoptosis and expression of cyclooxygenase-2 in the corpus luteum of female rats with thyroid dysfunction. These processes may be important in understanding the reproductive changes caused by thyroid dysfunction. A total of 18 adult female rats were divided into three groups (control, hypothyroid and hyperthyroid) with six animals per group. Three months after treatment to induce thyroid dysfunction, the rats were euthanized in the dioestrus phase. The ovaries were collected and immunohistochemically analysed for expression of the cell proliferation marker CDC-47, vascular endothelial growth factor (VEGF), VEGF receptor Flk-1 and cyclooxygenase-2 (COX-2). Apoptosis was evaluated using the TUNEL assay. Hypothyroidism reduced the intensity and area of COX-2 expression in the corpus luteum (p < 0.05), while hyperthyroidism did not alter COX-2 expression in the dioestrus phase. Hypothyroidism significantly reduced the expression of CDC-47 in endothelial cells and pericytes in the corpus luteum, whereas hyperthyroidism did not induce a detectable change in CDC-47 expression (p > 0.05). Hypothyroidism reduced the level of apoptosis in luteal cells (p < 0.05) and increased VEGF expression in the corpus luteum. In contrast, hyperthyroidism increased the level of apoptosis in the corpus luteum (p < 0.05). In conclusion, thyroid dysfunction differentially affects the levels of proliferative activity, angiogenesis and apoptosis and COX-2 expression in the corpus luteum of female rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Corpus Luteum / chemistry
  • Corpus Luteum / pathology*
  • Corpus Luteum / physiopathology*
  • Cyclooxygenase 2 / analysis*
  • Female
  • Hyperthyroidism / chemically induced
  • Hyperthyroidism / pathology
  • Hyperthyroidism / physiopathology*
  • Hypothyroidism / chemically induced
  • Hypothyroidism / pathology
  • Hypothyroidism / physiopathology*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Minichromosome Maintenance Complex Component 7 / analysis
  • Neovascularization, Physiologic
  • Propylthiouracil / administration & dosage
  • Rats
  • Rats, Wistar
  • Thyroxine / administration & dosage
  • Thyroxine / blood
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor Receptor-2 / analysis

Substances

  • Vascular Endothelial Growth Factor A
  • Propylthiouracil
  • Cyclooxygenase 2
  • Vascular Endothelial Growth Factor Receptor-2
  • MCM7 protein, rat
  • Minichromosome Maintenance Complex Component 7
  • Thyroxine