Study on physical development and neuroethological development of offspring by frozen embryo transfer

• Project/Area Number: 17K09188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Tohoku University
• Principal Investigator: Miyauchi Naoko 東北大学, 医学系研究科, 技術補佐員 (60596162)
• Project Period (FY): 2018-02-28 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 不妊治療 / 胚盤胞移植（FET） / 低分子RNA（miRNA） / 胎盤 / 胚盤胞移植 / 性比 / 一卵性双胎 / 低分子RNA / 母子保健

Outline of Final Research Achievements

Recently, attention has been focused on the relationship between assisted reproductive technology (ART) and neuropsychiatric developmental disorders in the offsprings. In this study, the effects of ART on the offsprings were compared by epidemiological studies and epigenome analyses of the placenta. As a result, blastocyst transfer affects the sex ratio and the frequency of occurrence of monozygotic twins, and that there were small RNAs that are specifically changed in the placenta by frozen embryo transfer. These results suggested that the ART coved affect the epigenome of the offspring.

Academic Significance and Societal Importance of the Research Achievements

本研究では、疫学調査の結果に基づき、ART、特に凍結胚移植の出生児への性差及び一卵性双胎の頻度において影響がみられることが判明した。またART由来の胎盤組織のエピゲノム解析により、影響を受けやすい遺伝子領域を明らかにし、科学的な検証を行い、不妊治療の影響を安全性とリスクの両面で評価することができた。これらの成果は、ARTによる胚発生過程におけるエピゲノムの変動が生じやすいことや変化が継承され胎児へその特性が移行するなど学術的な意義の存在と社会的意義の存在が示唆された。将来の自閉症や行動異常などへの傾向についても予測することができ、今後の研究継続の必要性を痛感した。

Research Products

• [Journal Article] Association of four imprinting disorders and ART (2019)
  • Author(s): Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
  • Journal Title: Clin Epigenetics Volume: 11 Issue: 1 Pages: 21-21
  • DOI: 10.1186/s13148-019-0623-3
  • Peer Reviewed / Open Access
• [Journal Article] The risk of secondary sex ratio imbalance and increased monozygotic twinning after blastocyst transfer: data from the Japan Environment and Children’s Study (2019)
  • Author(s): Hattori Hiromitsu、Kitamura Akane、Takahashi Fumiaki、Kobayashi Norio、Sato Akiko、Miyauchi Naoko、Nishigori Hidekazu、Mizuno Satoshi、Sakurai Kasumi、Ishikuro Mami、Obara Taku、Tatsuta Nozomi、Nishijima Ichiko、Fujiwara Ikuma、Kuriyama Shinichi、Metoki Hirohito、Yaegashi Nobuo、Nakai Kunihiko、Arima Takahiro
  • Journal Title: Reproductive Biology and Endocrinology Volume: 17 Issue: 1 Pages: 27-27
  • DOI: 10.1186/s12958-019-0471-1
  • Peer Reviewed / Open Access
• [Journal Article] The risk of secondary sex ratio imbalance and increased monozygotic twinning 1 after blastocyst transfer: data from The Japan Environment and Children’s Study. (2019)
  • Author(s): Hattori H, Kitamura A, Takahashi F, Kobayashi N, Sato A, Miyauchi N, Nishigori H, Mizuno S, Sakurai K, Ishikuro M, Obara T, Tatsuta N, Nishijima I, Fujiwara I, Kuriyama S, Metoki H, Yaegashi N, Nakai K, Arima T, Japan Environment Childrenʼs Study Group.
  • Journal Title: Reproductive Biology and Endocrinology Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Association of four imprinting disorders and ART. (2019)
  • Author(s): Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
  • Journal Title: Clinical Epigenetics Volume: 印刷中
  • Open Access
• [Journal Article] Lack of association between receiving ART treatment and parental psychological distress during pregnancy: Preliminary findings of the Japan Environment and Children’s Study. (2018)
  • Author(s): Yoshimasu K, Tsuno K, Sato A, Miyauchi N, Yaegashi N, Nakai K, Arima T and Japan Environment Children’s Study Group.
  • Journal Title: Biomedicine & Society.ｖ Volume: 5 Pages: 5-16
  • Peer Reviewed / Open Access
• [Book] ART治療における遺伝的安全性とリスク (2019)
  • Author(s): 宮内尚子、服部裕充、小林記緒、樋浦仁、有馬隆博
  • Total Pages: 4
  • Publisher: ニューサイエンス社