Molecular Mechanisms of Progesterone Receptor Signaling to Maintain Pregnancy and Induce Preterm Birth by Disruption

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18204
• 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: Nippon Medical School
• Principal Investigator: Sugita Yosuke 日本医科大学, 医学部, 助教 (60774354)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 早産 / 子宮頸管無力症 / 子宮頸管縫縮術 / プロゲステロン

Outline of Final Research Achievements

To elucidate the mechanism of pregnancy maintenance by progesterone (P4) signaling in the cervix, we established cervical fibroblast culture lines from patients with different clinical backgrounds and compared P4 responses. Cervical tissue samples were obtained from patients with refractory cervical insufficiency (CI) who underwent transabdominal cervical suture and maintained pregnancy, and from controls with cervical immaturity, respectively, at the time of cesarean section. Analysis of the changes caused by the addition of P4 to the cultured cells showed that the P4 response observed in the immature cases was attenuated in CI. Furthermore, we analyzed the expression of P4 receptor (PR) by real-time PCR, Western blotting, and cell immunostaining, and found that PR was significantly decreased in CI.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

原因不明であった難治性子宮頸管無力症において、プロゲステロン受容体の発現低下に起因するプロゲステロン応答の破綻が原因の一因となっていることが示唆された。新たな早産治療戦略の礎となりうる重要な知見を得た。