The effects of stress response system in the ovary: KEAP1-NRF2 system and female infertility

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07361
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: MATSUMARU Daisuke 岐阜薬科大学, 薬学部, 准教授 (50624152)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 卵巣 / 酸化ストレス / 炎症 / 卵胞 / 細胞死 / 細胞増殖

Outline of Final Research Achievements

The ovarian functions are strongly affected by aging. Therefore, infertility has become an emerging social problem by recent late marriages. Generally, the presence of excessive oxidative stress in the ovary is explained as a cause of female infertility, but the mechanisms how it causes infertility remain unclear. The current study analyzed the effects of aging, oxidative stress, and stress response systems on ovarian function. We utilized aged mice and genetically modified mice showing symptoms similar to polycystic ovary syndrome (PCOS). In the aged mice, we observed histological abnormalities in the ovary and an increase of oxidative stress markers. In the PCOS model mice, we observed abnormal ovarian follicle morphology, inflammation, and increased oxidative stress markers. An antioxidant treatment improved part of such ovarian abnormalities. These results suggest that oxidative stress and its response systems, at least in part, play an essential role in infertility.

Free Research Field

生殖内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、加齢と酸化ストレスが卵巣機能に与える影響を解析し、またPCOS（多嚢胞性卵巣症候群）の発症メカニズムを探ることを目的とした解析を行った。研究成果として、卵巣の加齢に伴う組織像の変化や酸化ストレスの関与を示唆し、PCOSモデルマウスにおける酸化ストレス応答、炎症の存在を示した。抗酸化剤を用いて部分的な症状回復を誘導できた点から、酸化ストレスの制御が不妊治療のアプローチの1つとなりうる可能性が示唆された。