Inflammetory cytokines-induced HIF-1 activation confers the epithelial-to-mesenchymal cell differentiation in endometrial epithelial cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kansai Medical University
• Principal Investigator: NAKAO Tomoko 関西医科大学, 医学部, 講師 (00465642)
• Co-Investigator(Kenkyū-buntansha): 岡田 英孝 関西医科大学, 医学部, 教授 (80330182)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 子宮内膜環境 / HIF-1 / 低酸素 / 炎症 / 着床

Outline of Final Research Achievements

The partial pressure of oxygen in the endometrium is highly variable, thus mandating the investigation of the involvement of hypoxia-inducible factors (HIFs) in endometrial tissue. On the other hand, there are various phenomena that cannot be explained by the classical dogma that "HIF activation = hypoxia," and one of the key words is inflammation. The purpose of this study is to demonstrate the interrelationship between intrauterine oxygenation, HIF, and inflammation, and to analyze their effects on the differentiation and function of endometrial cells. Recently, the focus has been on the relationship between chronic endometritis and implantation disorders, and epithelial-mesenchymal transition(EMT) is thought to play an important role during implantation. In this study, we found that HIF and EMT-inducing factors were induced by inflammatory cytokines and hypoxia. This result suggests that HIF and EMT-inducing factors induced by chronic endometritis may affect implantation function.

Free Research Field

子宮内膜

Academic Significance and Societal Importance of the Research Achievements

慢性子宮内膜炎は不妊症の原因になると考えられている。細菌感染や種々の要因による反応性過程と考えられているが、画一された診断基準がなく、病態についても解明されていない点が多い。治療として抗菌薬やプロバイオティクスの投与が行われているが、明確な効果判定法もなく、その後の不妊治療成績への寄与も不明である。今回我々は子宮内酸素環境-HIF-1-炎症の相互関係に着目し、炎症性サイトカインおよび低酸素症に誘導されるHIFおよびEMT因子が着床機能に影響を与える可能性を示すことにより、慢性子宮内膜炎の病態解明につなげることができた。