A role of endoplasmic reticulum stress in ovarian angiogenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: Harada Miyuki 東京大学, 医学部附属病院, 講師 (70451812)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 卵巣 / 血管新生 / 小胞体ストレス応答

Outline of Final Research Achievements

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 non-OHSS patients. The ER stress inducer tunicamycin increased hCG-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. Our findings suggest ER stress upregulates hCG-induced VEGFA production in granulosa cells, indicating that ER stress might be involved in OHSS development.

Free Research Field

生殖内分泌学