Effects and mechanism of action of PDE5 inhibitors on a mouse model of endometrial thinning

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18164
• 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: Mie University
• Principal Investigator: Nishioka Mikiko 三重大学, 医学系研究科, リサーチアソシエイト (20770267)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 着床不妊 / 子宮内膜菲薄化モデルマウス / Phosphodiesterase5阻害薬 / Tadalafil

Outline of Final Research Achievements

Infertility treatment is a pressing issue in Japan, where the birthrate is declining and the population is aging, but the pregnancy rate through in vitro fertilization remains at 30%. Endometrial thinning, one of the causes of implantation factor infertility, has been shown to improve and increase the implantation rate with the use of Sildenafil, a phosphodiesterase (PDE)5 inhibitor, but side effects remain a problem. The study established a method to generate a mouse model of endometrial thinning and examined whether Tadalafil, a third-generation drug with fewer side effects, could improve the thinning, but no improvement in thinning was observed. Considering cell depletion as a possible cause, they transplanted dispersed uterine cells from another individual, which resulted in restoration of endometrial tissue.

Free Research Field

生殖内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、エタノール投与による子宮内膜菲薄化モデルマウスの作製法を確立し、Tadalafilの効果を確認するためにはモデルマウスへの細胞の補充が必要であることが判明した。今後モデルマウスへの移植する細胞数の最適化が必要であるが、最適化されれればTadalafilの効果が確認できると考えられ、将来的にはPDE5阻害薬による菲薄化の改善に関わる作用機序の一端が解明できることが期待される。また不妊治療において、一定数存在する子宮内膜菲薄化による着床不妊のち治療法開発などへの応用も期待でき社会的な意義も大きいと考えられる。