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Maternal Genetic Background of Infectious Preterm Birth

Research Project

Project/Area Number 17H04237
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionOsama Woman's and Children's Hospital

Principal Investigator

Yanagihara Itaru  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 免疫部門, 部長 (60314415)

Co-Investigator(Kenkyū-buntansha) 林 克彦  九州大学, 医学研究院, 教授 (20287486)
西海 史子  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 免疫部門, 流動研究員 (60599596)
呉 恒寧  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 免疫部門, 研究技術員 (80648139)
吉村 芳修  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 免疫部門, 研究員 (90771197)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords早産 / 流産 / ウレアプラズマ / 卵母細胞再構築系 / メチル化酵素 / 卵母細胞培養 / 感染性流早産 / 再構築卵母細胞 / 人工卵巣 / 始原生殖細胞様細胞 / 精子機能 / 卵母細胞分化誘導系 / iPS / ES/iPS / 卵子形成過程再構築 / iPSマウス卵母細胞分化
Outline of Final Research Achievements

A cross-sectional study on 243 patients presenting with pregnancy loss for the degree of intervillous fibrin, intervillous thrombosis (IT), decidual fibrin, and decidual thrombosis (DT), and their MTHFR C677T genotype were determined. There were significantly more T allele carriers and TT genotype cases among patients with severe IT, and those with severe IT and DT (OR 2.6, P P=0.032). The CC genotype was protective against the studied pathological grades. This study is the first study showing that the MTHFR TT genotype and T allele are associated with severe intervillous and decidual pathologies in patients with pregnancy loss.
The severity and incidence of infantile bronchopulmonary dysplasia (BPD) were assessed after maternal antibiotic treatments. The frequency of severe BPD in the ampicillin-sulbactam with azithromycin group was significantly lower than that in the other group, even when adjusted for gestational age at the time of rupture of membrane, with an odds ratio of 0.02.

Academic Significance and Societal Importance of the Research Achievements

我が国における流早産原因菌のウレアプラズマの疫学、病原性、薬剤耐性、ゲノム配列などを報告してきた。これら解析の目的は臨床的な流産、早産のメカニズムを明らかにし、不可逆的な早産合併症である新生児慢性肺疾患や、神経障害を如何に減少させることにある。今回の我々の臨床研究における解析結果は、1)重症新生児慢性肺疾患の頻度を低下される母体への抗菌薬投与プロトコルを検証し、早産合併症制御法を確立したこと、そして2)母親の遺伝的背景が流産胎盤病理と関連することを見出したことにある。このことは新たな不育症への治療の手がかりを示すもので葉酸治療の有効性を示唆した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (50 results)

All 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (30 results) (of which Invited: 5 results) Remarks (2 results)

  • [Int'l Joint Research] フィリピン大学マニラ校(フィリピン)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] J Craig Venter Institute/New England Biolobs(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] フィリピン大学マニラ校(フィリピン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ソフィアテクニカル大学(ブルガリア)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures.2019

    • Author(s)
      Inagaki H, Ota S, Nishizawa H, Miyamura H, Nakahira K, Suzuki M, Nishiyama S, Kato T, Yanagihara I, Kurahashi H.
    • Journal Title

      J Hum Genet.

      Volume: 64 Issue: 5 Pages: 459-466

    • DOI

      10.1038/s10038-019-0578-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New antibiotic regimen for preterm premature rupture of membrane reduces the incidence of bronchopulmonary dysplasia.2019

    • Author(s)
      Tanaka S, Tsumura K, Nakura Y, Tokuda T, Nakahashi H, Yamamoto T, Ono T, Yanagihara I, Nomiyama M
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 45 Issue: 5 Pages: 967-973

    • DOI

      10.1111/jog.13903

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case series of the dynamics of lipid mediators in patients with sepsis.2019

    • Author(s)
      Hamaguchi M, Wu HN, Tanaka M, Tsuda N, Tantengco OAG, Matsushima T, Nakao T, Ishibe T, Sakata I, Yanagihara I.
    • Journal Title

      Acute Med Surg.

      Volume: 20 Issue: 4 Pages: 2103-2107

    • DOI

      10.1002/ams2.443

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Toxoplasma gondii strain isolated in Okinawa, Japan shows high virulence in Microminipigs.2019

    • Author(s)
      Taniguchi Y, Yanagihara I, Nakura Y, Ichikawa C, Saito T, Appiah-Kwarteng C, Matsuzaki M, Fukumoto J, Nagamune K, Kyan H, Takasu M, Kitoh K, Takashima Y.
    • Journal Title

      Parasitol Int

      Volume: 72 Pages: 101935-101935

    • DOI

      10.1016/j.parint.2019.101935

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of PIK3CA and MDM2 SNP309 with Cervical Squamous Cell Carcinoma in a Philippine Population.2019

    • Author(s)
      Tantengco OAG, Nakura Y, Yoshimura M, Llamas-Clark EF, Yanagihara I.
    • Journal Title

      Asian Pac J Cancer Prev.

      Volume: 20 Issue: 7 Pages: 2103-2107

    • DOI

      10.31557/apjcp.2019.20.7.2103

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Current understanding and treatment of intra-amniotic infection with Ureaplasma spp.2019

    • Author(s)
      Tantengco OAG, Yanagihara I.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 45 Issue: 9 Pages: 1796-1808

    • DOI

      10.1111/jog.14052

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fatal overwhelming postsplenectomy due to Streptococcus pneumoniae serotype 10A with atypical polysaccharide capsule in a patient with chromosome 22q11.2 deletion syndrome: A case report. J Infect Chemother2019

    • Author(s)
      Matsuoka K, Yanagihara I, Takeuchi M, et al.
    • Journal Title

      J Infect Chemother

      Volume: 25 Issue: 3 Pages: 192-196

    • DOI

      10.1016/j.jiac.2018.07.015

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of maternal methylenetetrahydrofolate reductase C677T polymorphism on intervillous and decidual pathology with pregnancy loss.2019

    • Author(s)
      Mehandjiev TR, Tenno NM, Yanagihara I, et al.,
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 45 Issue: 1 Pages: 78-85

    • DOI

      10.1111/jog.13798

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Type II restriction modification system in Ureaplasma parvum OMC-P162 strain2018

    • Author(s)
      Wu Heng Ning、Nakura Yukiko、Yoshimura Michinobu、Gaddi Tantengco Ourlad Alzeus、Nomiyama Makoto、Takayanagi Toshimitsu、Fujita Tomio、Yasukawa Kiyoshi、Yanagihara Itaru
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 10 Pages: 0205328-0205328

    • DOI

      10.1371/journal.pone.0205328

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid and simple detection of Ureaplasma species from vaginal swab samples using a loop-mediated isothermal amplification method.2018

    • Author(s)
      Fuwa K, Seki M, Hirata Y, Yanagihara I, Nakura Y, Takano C, Kuroda K, Hayakawa S.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 79 Issue: 1 Pages: 1-8

    • DOI

      10.1111/aji.12771

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High sensitive RNA detection by one-step RT-PCR using the genetically engineered variant of DNA polymerase with reverse transcriptase activity from hyperthermophilies.2018

    • Author(s)
      Okano H, Baba M, Kawato K, Hidese R, Yanagihara I, Kojima K, Takita T, Fujiwara S, Yasukawa K.
    • Journal Title

      J Biosci Bioeng.

      Volume: 125 Pages: 275-281

    • NAID

      40021507439

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Next-generation sequencing-based analysis of reverse transcriptase fidelity.2017

    • Author(s)
      Yasukawa K, Iida K, Okano H, Hidese R, Baba M, Yanagihara I, Kojima K, Takita T, Fujiwara S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 492 Pages: 147-153

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High sensitive one-step RT-PCR using MMLV reverse transcriptase, DNA polymerase with reverse transcriptase activity, and DNA/RNA helicase.2017

    • Author(s)
      Okano H, Baba M, Yamasaki T, Hidese R, Fujiwara S, Yanagihara I, Ujiiye T, Hayashi T, Kojima K, Takita T, Yasukawa K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 487 Pages: 128-133

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular fate of Ureaplasma parvum entrapped by host cellular autophagy2017

    • Author(s)
      Nishiumi F, Ogawa M, Nakura Y, Hamada Y, Nakayama M, Mitobe J, Hiraide A, Sakai N, Takeuchi M, Yoshimori T, Yanagihara I*
    • Journal Title

      MicrobiologyOpen

      Volume: - Issue: 3 Pages: 1-15

    • DOI

      10.1002/mbo3.441

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] トキソプラズマ国内分離株のブタにおける病原性2019

    • Author(s)
      谷口裕二、柳原格、名倉由起子、松崎素道、福本隼平、喜屋武向子、鬼頭克也、永宗喜三郎、高島康弘
    • Organizer
      第88回日本寄生虫学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 改良された次世代シークエンスによる逆転写酵素の正確性の解析2019

    • Author(s)
      岡野啓志、馬場美聡、秀瀬涼太、飯田慶、李瞳陽、兒島憲二、滝田禎亮、柳原格、藤原伸介、保川清
    • Organizer
      日本農芸化学会2019年大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 赤痢菌の細胞骨格蛋白RodZの多量体形成機構と局在の解析2019

    • Author(s)
      三戸部 治郎、西海 史子、柳原 格、大西 真
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Ureaplasma parvum OMC-P162株に存在する新規制限修飾系2019

    • Author(s)
      呉恒寧、名倉由起子、吉村芳修、柳原格
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウレアプラズマとヒト流早産2019

    • Author(s)
      柳原格
    • Organizer
      第46回日本マイコプラズマ学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Ureaplasma parvum のマウス精子への影響2019

    • Author(s)
      伊東 和俊、西海 史子、名倉 由起子、呉 恒寧、吉村 芳修、柳原 格
    • Organizer
      第46回日本マイコプラズマ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Ureaplasma parvum OMC-P162 株に存在する新規制限修飾系2019

    • Author(s)
      呉 恒寧、名倉 由起子、吉村 芳修、柳原 格
    • Organizer
      第46回日本マイコプラズ学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 切迫早産とウレアプラズマ2019

    • Author(s)
      脇本哲、呉恒寧、柳原格
    • Organizer
      第39回近畿腸管微生物研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Serratia marcescens 感染による2絨毛膜2羊膜双胎流産胎盤の解析2019

    • Author(s)
      名倉由起子 、川口晴菜 、山本亮、竹内真 、石井桂介 、柳原格
    • Organizer
      第55回日本周産期・新生児医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新生児慢性肺疾患児が幼児期にリューマチ因子を産生する2019

    • Author(s)
      北島博之、 藤村正晢、佐藤真穂、中山雅弘、竹内真、名倉由起子、柳原 格
    • Organizer
      第55回日本周産期・新生児医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 早産児III型慢性肺疾患児ではウレアプラズマ胎内感染が致死的肺高血圧症を引き起こす可能性がある2019

    • Author(s)
      北島博之、藤村正哲、中山雅弘、竹内 真、名倉由起子、平田克弥、平野慎也、和田和子、柳原格
    • Organizer
      第55回日本周産期・新生児医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウレアプラズマ~最小生物の脅威~2019

    • Author(s)
      柳原格
    • Organizer
      第64回日本新生児成育医学会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] トキソプラズマ国内分離株のブタにおける病原性2019

    • Author(s)
      谷口裕二、柳原格、名倉由起子、松崎素道、福本隼平、喜屋武向子、鬼頭克也、永宗喜三郎、高島康弘
    • Organizer
      第88回日本寄生虫学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pathogenesis of Ureaplasma infection in perinatal and neonatal medicine2018

    • Author(s)
      Michinobu Yoshimura, Fumiko Nishiumi, Heng Ning Wu, Yukiko Nakura, Itaru Yanagihara
    • Organizer
      The Joint Congress of the 7th Meeting of the Asian Organization for Mycoplasmology (AOM) and the 45th Meeting of Japanese Society of Mycoplasmology (JSM)
    • Related Report
      2018 Annual Research Report
  • [Presentation] TypeⅡrestriction modification system in Ureaplasma parvum OMC-P162 strain2018

    • Author(s)
      Heng Ning Wu, Yukiko Nakura, Michinobu Yoshimura, Itaru Yanagihara
    • Organizer
      The Joint Congress of the 7th Meeting of the Asian Organization for Mycoplasmology (AOM) and the 45th Meeting of Japanese Society of Mycoplasmology (JSM)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高病原性オウム病病原体の遺伝子解析2018

    • Author(s)
      名倉由起子、清水可奈子、河原和美、竹内真、吉田好雄、柳原格
    • Organizer
      第54回日本周産期・新生児医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Screening of DNA aptamers against synthetic lipopeptide UPM-1for Ureaplasma detection2018

    • Author(s)
      Jeany Meza,Maui Nishio, Kaori Tsukakoshi, Itaru Yanagihara, Kenichiro Hata, Kazuhiko Nakahashi, Kazunori Ikebukuro
    • Organizer
      日本核酸化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 気管内ウレアプラズマ(U)検出に母体および児へのAZM投与が及ぼす影響について2018

    • Author(s)
      江頭政和、冨野広道、川端祥平、七條了宣、飯田千晶、江頭智子、水上朋子、高柳俊光、柳原格
    • Organizer
      第63回日本新生児育成医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 母児へのウレアプラズマ(U)介入前後における超早産児の臨床像の比較検討2018

    • Author(s)
      江頭政和、冨野広道、川端祥平、七條了宣、飯田千晶、江頭智子、水上朋子、高柳俊光、柳原格
    • Organizer
      第63回日本新生児育成医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Next-generation sequencing-based analysis of reverse transcriptase fidelity2018

    • Author(s)
      Kiyoshi Yasukawa, Hiroyuki Okano, Misato Baba, Kei Iida, Ryota Hidese, Itaru Yanagihara, Kenji Kojima, Teisuke Takita, Shinsuke Fijiwara
    • Organizer
      BICON
    • Related Report
      2018 Annual Research Report
  • [Presentation] ウレアプラズマUP162株の全ゲノム解析2017

    • Author(s)
      呉恒寧、名倉由起子、吉村芳修、柳原格
    • Organizer
      第44回日本マイコプラズマ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Ureaplasma parvum 感染細胞からのU. parvum放出と二次感染メカニズムの解明2017

    • Author(s)
      西海史子、柳原格
    • Organizer
      第44回日本マイコプラズマ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ウレアプラズマとヒトの流早産2017

    • Author(s)
      柳原格
    • Organizer
      第44回日本マイコプラズマ学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血球貪食症候群を伴った患者由来胎盤からの微生物検索2017

    • Author(s)
      吉村芳修、名倉由起子、柳原格
    • Organizer
      第37回近畿腸管微生物研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 死亡妊婦からのオウム病病原体の検出2017

    • Author(s)
      柳原格
    • Organizer
      第35回日本クラミジア研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ワクチン含有血清型肺炎球菌による脾臓摘出術後重症感染症で死亡した22q11.2欠失症候群の検討2017

    • Author(s)
      伊東和俊、松岡圭子、名倉由起子、河津由紀子、佐藤真穂、川田博昭、明田幸宏、竹内真、柳原格
    • Organizer
      第49回日本小児感染症学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 妊婦、胎児死亡例の胎盤におけるオウム病病原体遺伝子の同定2017

    • Author(s)
      柳原格、吉村芳修、清水可奈子、名倉由起子、河原和美、竹内真、今村好章、吉田好雄
    • Organizer
      第63回日本病理学会コンパニオンミーティング
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Rapid and simple detection of Ureaplasma species from vaginal swab samples using Loop-Mediataed Isothermal Amplification method2017

    • Author(s)
      Kazumasa Fuwa, Chika Takano, Mitsuko Seki, Kazumichi Kuroda, Yoshiyasu Hirata, Itaru Yanagihara, Satoshi Hayahkawa
    • Organizer
      Pediatric Academic Society Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Vibrio vulnificus bacteriolysis was caused by hydrogen Peroxide.2017

    • Author(s)
      Michinobu Yoshimura, Shin-ichi Yoshida, Itaru Yanagihara
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) 19th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim
    • Related Report
      2017 Annual Research Report
  • [Presentation] Epidemiologic, Microbiologic and Genetic Characterization of Ovarian Cancer among Filipino Patients in Philippine General Hospital2017

    • Author(s)
      Ana Joy Padua, Jose Nevado Jr, Erlidia Llamas-Clark, Yukiko Nakura, Itaru Yanagihara
    • Organizer
      EMBO/EMBL symposium
    • Related Report
      2017 Annual Research Report
  • [Remarks] 大阪母子医療センター研究所免疫部門

    • URL

      https://www.wch.opho.jp/research/developmental/index.html

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 大阪母子医療センター研究所免疫部門

    • URL

      http://www.mch.pref.osaka.jp/research/developmental/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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