Brain damage and developmental defects in a mouse model of high-dose oxytocin oxytocin induced delivery

• Project/Area Number: 18K09237
• 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: Juntendo University
• Principal Investigator: ITAKURA ATSUO 順天堂大学, 医学部, 教授 (70262897)
• Co-Investigator(Kenkyū-buntansha): 平山 貴士 順天堂大学, 医学部, 助教 (20816962) ; 小池 正人 順天堂大学, 大学院医学研究科, 教授 (80347210)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: オキシトシン / 自閉症スペクトラム障害 / 分娩誘発 / 脳障害 / マウス / 脳性麻痺 / 分娩 / 陣痛

Outline of Final Research Achievements

In the present study, following a previous study, we performed a detailed analysis of brain damage in the prefrontal cortex of neonatal mouse pups induced by high-dose oxytocin (OXT)-induced parturition. Cell death was observed in the inferior and anterior limbic cortices of the ventral medial prefrontal cortex and in the cerebrospinal forceps in male pups born after high-dose OXT induction. These areas have been implicated in the autism spectrum, suggesting that they are susceptible to brain damage in male pups born after high-dose OXT-induced delivery.

Academic Significance and Societal Importance of the Research Achievements

オキシトシンは分娩誘発・促進剤として産科の処置で一般的に使用される薬剤であり、有害事象として過剰な子宮収縮によって、胎児へ低酸素性脳症などの有害事象が発生することが知られている。母獣への高用量でのオキシトシン投与は、過剰な子宮収縮を誘発させた今回の解析で影響を受けた領域は、自閉症スペクトラム障害など精神発達障害に関連する部位であった。疫学調査で分娩時オキシトシンを使用した児に精神発達障害が多いとの報告も見られ、オキシトシンによる過剰な子宮収縮と自閉症スペクトラム障害発症の関係があることが示唆された。

Research Products

• [Journal Article] Susceptibility of subregions of prefrontal cortex and corpus callosum to damage by high-dose oxytocin-induced labor in male neonatal mice (2021)
  • Author(s): Kitamura Eri、Koike Masato、Hirayama Takashi、Sunabori Takehiko、Kameda Hiroshi、Hioki Hiroyuki、Takeda Satoru、Itakura Atsuo
  • Journal Title: PLOS ONE Volume: 16 Issue: 8 Pages: e0256693-e0256693
  • DOI: 10.1371/journal.pone.0256693
  • Peer Reviewed / Open Access
• [Journal Article] Oxytocin induced labor causes region and sex-specific transient oligodendrocyte cell death in neonatal mouse brain. (2020)
  • Author(s): Hirayama, T., Hiraoka, Y., Kitamura, E., Miyazaki, S., Horie, K., Fukuda, T., Hidema, S., Koike, M., Itakura, A., Takeda S.
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 141(46) Pages: 66-78
  • Peer Reviewed / Open Access