Fetal signal-mediated maintenance of intrauterine environment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08307
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Tokai University
• Principal Investigator: ISHIMOTO HITOSHI 東海大学, 医学部, 教授 (10212937)
• Co-Investigator(Kenkyū-buntansha): 亀谷 美恵 東海大学, 医学部, 准教授 (50338787) ; 後藤 優美子 東海大学, 医学部, 講師 (50624574) ; 宮澤 昌樹 東海大学, 医学部, 客員講師 (30624572) ; 柏木 寛史 東海大学, 医学部, 助教 (10710460) ; 宮澤 麻里子 東海大学, 医学部, 特定研究員 (80637091)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 羊膜 / 胎児肺

Outline of Final Research Achievements

In search for fetal factors involved in the maintenance of fetal membranes, we studied on midkine (MDK) that shows fetus-specific expression. Obtained data is as follows: 1) in human amniotic epithelial cells, MDK did not change mRNA expression of progesterone-related factors including PGR, PGRMC1, PGRMC2, SRD5A1, AKR1C1, AKR1C2, AKR1C3, AKR1D1, and HSD17B2; 2) MDK suppressed ADM mRNA expression in human amnion tissue, 3) in human fetal lung, MDK protein was localized in alveolar epithelial cells, and MDK staining intensity and MDK mRNA expression in the lung were remarkably low at over 32 weeks of gestation compared to those at earlier weeks, 4) in A459 lung cells, dexamethasone decreased MDK mRNA expression in a dose-dependent manner; and 5) in NCI-H441 lung cells, addition of progesterone, at lower concentrations within physiological range for pregnant women, augmented MDK mRNA expression.

Free Research Field

周産期医学

Academic Significance and Societal Importance of the Research Achievements

今回の成果は「MDKは胎児肺で産生され、羊水中に出て羊膜に働きかけ妊娠維持に働く。そして妊娠末期に肺での産生と羊水中濃度が低下して分娩発来の一因となる」、という作業仮説において、肺と羊水中のMDK動態を説明しうるものであり、MDKが妊娠維持に働く胎児シグナルである可能性が高まったといえる。このような知見の積み上げは、妊娠維持機構の破綻（早産や前期破水など）の予防を模索する上で重要と考えられる。