A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome

Mol Cell Endocrinol. 2016 Jun 15:428:161-9. doi: 10.1016/j.mce.2016.03.032. Epub 2016 Mar 28.

Abstract

Vascular endothelial growth factor A (VEGFA) is crucial for ovarian angiogenesis, but its excess production induces ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine whether endoplasmic reticulum (ER) stress regulates VEGFA expression in granulosa cells, and whether its activation is involved in OHSS development. The expression of the spliced form of X-box-binding protein 1 [XBP1(S)], induced by ER stress, in cumulus cells from OHSS patients was higher than that in cumulus cells from non-OHSS patients. The ER stress inducer tunicamycin increased human chorionic gonadotropin-induced VEGFA production in human granulosa cells through the induction of XBP1(S), and pretreatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) abrogated the effect of tunicamycin. In OHSS model rats, TUDCA administration prevented the OHSS development, reducing ovarian VEGFA production. Our findings suggest ER stress upregulates hCG-induced VEGFA production in granulosa cells, indicating that ER stress might be involved in OHSS development.

Keywords: Endoplasmic reticulum stress; Ovarian hyperstimulation syndrome; Ovary; Unfolded protein response; Vascular endothelial growth factor A.

MeSH terms

  • Adult
  • Animals
  • Capillary Permeability / drug effects
  • Chorionic Gonadotropin / administration & dosage
  • Chorionic Gonadotropin / pharmacology
  • Cumulus Cells / drug effects
  • Cumulus Cells / metabolism
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress* / drug effects
  • Female
  • Humans
  • Luteal Cells / drug effects
  • Luteal Cells / metabolism
  • Ovarian Hyperstimulation Syndrome / genetics
  • Ovarian Hyperstimulation Syndrome / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Taurochenodeoxycholic Acid / pharmacology
  • Tunicamycin / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • X-Box Binding Protein 1 / metabolism

Substances

  • Chorionic Gonadotropin
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Tunicamycin
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine