Novel identification of the etiology of neonatal respiratory distress syndrome and its pathogenesis.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08261
• 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: Juntendo University
• Principal Investigator: Suzuki Mitsuyoshi 順天堂大学, 医学部, 准教授 (90449059)
• Co-Investigator(Kenkyū-buntansha): 三原田 賢一 熊本大学, 国際先端医学研究機構, 特別招聘教授 (40455366) ; 中野 聡 順天堂大学, 医学部, 非常勤助教 (70826453)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 新生児呼吸窮迫症候群 / オキシステロール / 胆汁酸

Outline of Final Research Achievements

It is widely believed that changes in the maternal environment during gestation have significant direct and indirect effects on the fetus, but the specific factors that contribute to fetal development are largely unknown. We found that pups born from Cyp27a1 homozygous mice develop respiratory distress syndrome and die soon after birth, regardless of the genotype of the pups themselves. Conversely, even if the fetuses were homozygous, no pups died if the mother was heterozygous. In addition, when Cyp27a1 homozygous embryos artificially inseminated with sperm from homozygous males and eggs from homozygous females were implanted in the uterus of putative parental mice, healthy newborn pups were obtained, leading to the conclusion that this abnormality was caused by the maternal environment.

Free Research Field

新生児学 小児栄養学 小児消化器・肝臓病学

Academic Significance and Societal Importance of the Research Achievements

新生児呼吸窮迫症候群の分子メカニズム解明のため、27-Hydroxycholesterol(27-HC)が肺発生に及ぼす影響を独自の交配モデルを用いて解明することを目的とする。(1) (27-HC欠乏が新生児呼吸窮迫症候群の原因となるという報告はこれまでになく、病態生理を解析する上で非常な有用な動物モデルになり得る。また、肺形成に関わる新規転写因子やコード遺伝子などの探索から肺形成メカニズムの一端が解明できれば、(2)肺サーファクタント分泌異常や脂質トランスポーター異常による先天性肺胞蛋白症など、これまで根本的治療が存在しない難治性肺疾患に対する治療アプローチが発見できる可能性がある。