Analysis of the pathophysiology of polycystic ovary syndrome with a focus on inter-organ relationships

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18217
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya University
• Principal Investigator: Osuka Satoko 名古屋大学, 医学系研究科, 准教授 (30778296)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多嚢胞性卵巣症候群

Outline of Final Research Achievements

We analyzed animal models and existing data to extract factors associated among organs in PCOS. Analysis of the model detected RBP4 as a hepatokine with altered gene expression in the liver and elevated serum levels. Analysis of oocytes showed activation of ribosome-related pathways, and RBP4 has also been reported to be associated with ribosome activation. In addition, analysis of existing data on the endometrium, the site of implantation, showed decreased expression of IGF-1 and activation of the TNFa pathway, which is suppressed by IGF-1 and activated by RBP4, suggesting that androgen action and increased RBP4 secretion from the liver in PCOS may contribute to metabolic disorders and infertility.

Free Research Field

不妊生殖

Academic Significance and Societal Importance of the Research Achievements

PCOS（多嚢胞性卵巣症候群）は、排卵障害による不妊症に加え、糖質・脂質代謝異常や、子宮体がん、妊娠時中の周産期合併症の増加にも関与する。女性の 10% 程度に認められるありふれた疾患であるにもかかわらず、病態の詳細は不明であり、現在は対症療法のみで根本的な治療法はない。近年 2 型糖尿病や脂質代謝異常などの疾患において、臓器連関（臓器間のネットワーク）の重要性が多数報告されている。本研究では、PCOSを全身性の疾患ととらえて多臓器の解析を行うことで、PCOSにおいても臓器間のネットワークがその病態に関与することを示唆、PCOSの病態の理解を深め、抜本的な治療法開発に寄与する可能性がある。