Analysis of effects of Caesarean section delivery on the neuro-development of babies.

• Project/Area Number: 17K10085
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nippon Medical School
• Principal Investigator: Nagano Masatoshi 日本医科大学, 医学部, 講師 (60271350)
• Co-Investigator(Kenkyū-buntansha): 鈴木 秀典 日本医科大学, 大学院医学研究科, 大学院教授 (30221328) ; 齋藤 文仁 日本医科大学, 医学部, 准教授 (20360175) ; 坂井 敦 日本医科大学, 医学部, 講師 (30386156) ; 肥後 心平 日本医科大学, 医学部, 講師 (50623922) ; 三ケ原 靖規 日本医科大学, 医学部, アシスタントスタッフ (20748636)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: オキシトシン / 自閉症 / 帝王切開 / 社会性 / 周産期 / 発達障害

Outline of Final Research Achievements

We examined the effect of Cesarean section delivery on offspring's behaviors in mice.
When the offspring grow up, social abnormality was observed both in male and female. Such changes were attenuated by perinatal oxytocin (OXT) treatment. Wild-type (WT) mice born to prenatal OXT-receptor antagonist treated dams showed similar behavioral changes in both sexes. On the other hand, wild-type mice born of OXT-KO dams, in vitro fertilized WT mouse embryos were implanted into OXT-KO female, showed similar behavioral changes in only male.
Thus, prenatal OXT exposure from dam affect the development of sociability of the offspring in mice, especially in male. (Scientific Reports, in press)

Academic Significance and Societal Importance of the Research Achievements

帝王切開による出産は手術による危険性もあるため、2015年にはWHOが「医学的に必要な場合に限る」旨の警告を行った。ただ、日本では近年、高齢出産や不妊治療後等の様々な背景から増加している。しかし、帝王切開による出産が胎児の発達に与える影響については不明な部分も多く、自閉症スペクトラム（ASD）が経膣分娩に比して2割ほど増加するという疫学的報告もあるが、具体的な因果関係を示すには到っていない。今回マウスを使った結果では帝王切開によって生まれた子供は成長後、オス、メス共に社会性の低下が認められた。マウスの結果がそのままヒトに当てはまるとは限らないが、ヒトでの影響を精査し、対応を考える必要があろう。

Research Products

• [Journal Article] Cesarean section delivery is a risk factor of autism-related behaviors in mice (2021)
  • Author(s): Masatoshi Nagano, Fumihito Saitow, Shinpei Higo, Makoto Uzuki, Yasunori Mikahara, Toshio Akimoto, Hitoshi Ozawa, Katsuhiko Nishimori, Hidenori Suzuki
  • Journal Title: Scientific Reports Volume: - Issue: 1 Pages: 8883-8883
  • DOI: 10.1038/s41598-021-88437-8
  • Peer Reviewed / Open Access
• [Journal Article] Critical roles of serotonin-oxytocin interaction during the neonatal period in social behavior in 15q dup mice with autistic traits (2018)
  • Author(s): Nagano Masatoshi、Takumi Toru、Suzuki Hidenori
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-8
  • DOI: 10.1038/s41598-018-32042-9
  • Peer Reviewed / Open Access
• [Journal Article] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice. (2017)
  • Author(s): Nakai N, Nagano M, Saitow F, Watanabe Y, Kawamura Y, Kawamoto A, Tamada K, Mizuma H, Onoe H, Watanabe Y, Monai H, Hirase H, Nakatani J, Inagaki H, Kawada T, Miyazaki T, Watanabe M, Sato Y, Okabe S, Kitamura K, Kano M, Hashimoto K, Suzuki H, Takumi T.
  • Journal Title: Sci Adv. Volume: 3(6) Issue: 6
  • DOI: 10.1126/sciadv.1603001
  • Peer Reviewed / Open Access
• [Presentation] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice. (2017)
  • Author(s): N. Nakai, M. Nagano, F. Saitow, Y. Watanabe, Y. Kawamura, A. Kawamoto, K. Tamada, H. Mizuma, H. Onoe, Y. Watanabe, H. Monai, H. Hirase, Jin. Nakatani, H. Inagaki, T. Kawada, T. Miyazaki, M. Watanabe, Y. Sato, S. Okabe, K. Kitamura, M. Kano, K. Hashimoto, T. Takumi, H. Suzuki.
  • Organizer: 日本神経科学大会
• [Presentation] 幼若期における脳内セロトニン濃度の正常化が自閉症スペクトラムモデルマウスの社会性を改善させた (2017)
  • Author(s): 永野昌俊、齋藤文仁、内匠透、鈴木秀典
  • Organizer: 日本動物学会
• [Presentation] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice. (2017)
  • Author(s): N. Nakai, M. Nagano, F. Saitow, Y. Watanabe, Y. Kawamura, A. Kawamoto, K. Tamada, H. Mizuma, H. Onoe, Y. Watanabe, H. Monai, H. Hirase, Jin. Nakatani, H. Inagaki, T. Kawada, T. Miyazaki, M. Watanabe, Y. Sato, S. Okabe, K. Kitamura, M. Kano, K. Hashimoto, H. Suzuki, T. Takumi.
  • Organizer: Society for Neuroscience Annual meeting
  • Int'l Joint Research