Analysis of maternal recognition through embryo-specific sugar antigen and its inducing mechanisms for embryo implantation and placentation

• Project/Area Number: 23390389
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University (2013); Kyoto University (2011-2012)
• Principal Investigator: FUJIWARA Hiroshi 金沢大学, 医学系, 教授 (30252456)
• Co-Investigator(Kenkyū-buntansha): IMAGAWA Kazuhiko 東京大学, 農学生命科学研究科, 准教授 (00291956) ; SATO Yukiyasu 京都大学, 医学(系)研究科(研究院), 助教 (00508236) ; NISHI Eiichiro 京都大学, 医学(系)研究科(研究院), 准教授 (30362528) ; FUJITA Jun 京都大学, 医学(系)研究科(研究院), 教授 (50173430) ; HATTORI Akira 京都大学, 薬学研究科(研究院), 准教授 (50300893) ; ARAKI Yoshihiko 順天堂大学, 医学(系)研究科(研究院), 准教授 (70250933)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 糖鎖抗原 / 胚認識 / 胚着床 / 胎盤形成 / 免疫細胞 / 樹状細胞

Research Abstract

This project was based on the hypothesis that embryo transmits the information of their presence to maternal immune system using degenerated products of zona pellucida (Dp-ZP). In this study, we examined the effects of Dp-ZP on immune cell function and the transmitting system to para-aortic lymph nodes, and the effects of peripheral immune cells, platelets and laeverin on endometrial and trophoblast functions. As results, we found that murine zona pellucida could activate immune cells. In addition, we observed that laeverin was secreted from chorionic villi at very early stage, showing the possibility that it is related with induction of immune tolerance in concert with HLA-G. These findings suggest that laeverin is a novel embryonic signal secreted from extravillous trophoblast that invades the uterus.

Research Products

• [Journal Article] Imatinib sensitizes endometrial cancer cells to cisplatin by targeting CD117-positive growth-competent cells (2014)
  • Author(s): Zhang X, Kyo S, Nakamura M, Mizumoto Y, Maida Y, Bono Y, Takakura M, Fujiwara H
  • Journal Title: Cancer Lett Volume: 345 Pages: 106-14
  • Peer Reviewed
• [Journal Article] Eph-ephrin A system regulates human choriocarcinoma-derived JEG-3 cell invasion (2013)
  • Author(s): Fujiwara H, Nishioka Y, Matsumoto, H Suginami K, Horie A, Tani H, Matsumura N, Baba T, Sato Y, Araki Y, Konishi I
  • Journal Title: Int J Gynecol Cancer Volume: 23 Pages: 576-82
  • Peer Reviewed
• [Journal Article] Eph-ephrin A system regulates human choriocarcinoma-derived JEG-3 cell invasion. (2013)
  • Author(s): Fujiwara H, Nishioka Y, Matsumoto, H Suginami K, Horie A, Tani H, Matsumura N, Baba T, Sato Y, Araki Y, Konishi I
  • Journal Title: Int J Gynecol Cancer. Volume: 23 Issue: 3 Pages: 576-582
  • DOI: 10.1097/igc.0b013e3182849e36
  • Peer Reviewed
• [Journal Article] Overexpression of TEX101, a potential novel cancer marker, in head and neck squamous cell carcinoma. (2013)
  • Author(s): Yoshitake H, Yokoi H, Ishikawa H, Maruyama M, Endo S, Nojima M, Yoshida K, Yoshikawa H, Suzuki F, Takamori K, Fujiwara H, Araki Y
  • Journal Title: Cancer Biomarkers Volume: 12 Issue: 3 Pages: 141-148
  • DOI: 10.3233/cbm-130302
  • Peer Reviewed
• [Journal Article] Overexpression of TEX101, a potential novel cancer marker, in head and neck squamous cell carcinoma (2013)
  • Author(s): Yoshitake H, Yokoi H, Ishikawa H, Maruyama M, Endo S, Nojima M, Yoshida K, Yoshikawa H, Suzuki F, Takamori K, Fujiwara H, Araki Y
  • Journal Title: Cancer Biomark Volume: 12 Pages: 141-8
  • Peer Reviewed
• [Journal Article] Overexpression of TEX101, a potential novel cancer marker, in head and neck squamous cell carcinoma (2012)
  • Author(s): Yoshitake H, Yokoi H, Ishikawa H, Maruyama M, Endo S, Nojima M, Yoshida K, Yoshikawa H, Suzuki F, Takamori K, Fujiwara H, Araki Y
  • Journal Title: Cancer Biomarkers Volume: 2 Pages: 141-8
  • Peer Reviewed
• [Journal Article] Management of fetal death with placenta previa (2012)
  • Author(s): Taki M, Sato Y, Kakui K, Tatsumi K, Fujiwara H, Konishi I
  • Journal Title: J Matern Fetal Neonatal Med Volume: 25 Pages: 196-9
  • NAID: 120005385895
  • Peer Reviewed
• [Journal Article] Alterations of circulating endothelial cell and endothelial progenitor cell counts around the ovulation (2012)
  • Author(s): Tanaka S, Ueno T, Sato F, Chigusa Y, Kawaguchi-Sakita N, Kawashima M, Fujisawa N, Yoshimura K, Teramukai S, Fujiwara H, Fujita M, Toi M
  • Journal Title: J Clin Endocrinol Metab Volume: 97 Pages: 4182-92
  • NAID: 120005385897
  • Peer Reviewed
• [Journal Article] Laeverin/aminopeptidase Q induces trophoblast invasion during human early placentation (2012)
  • Author(s): Horie A, Fujiwara H, Sato Y, Suginami K, Matsumoto H, Maruyama M, Konishi I, Hattori A
  • Journal Title: Hum Reprod Volume: 27 Pages: 1267-76
  • Peer Reviewed
• [Journal Article] Mechanism of maternal vascular remodeling during human pregnancy (2012)
  • Author(s): Sato Y, Fujiwara H and Konishi I
  • Journal Title: Reprod Med Biol Volume: 11 Pages: 27-36
  • NAID: 10030444750
  • Peer Reviewed
• [Journal Article] EphrinA1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells (2011)
  • Author(s): Fujii H, Fujiwara H, Horie A, Suginami K, Sato Y, Konishi I
  • Journal Title: Hum Reprod Volume: 26 Pages: 1163-7
  • Peer Reviewed
• [Journal Article] Ephrin A1 induces intercellular dissociation in Ishikawa cells : possible implication of the Eph-ephrin A system in human embryo implantation (2011)
  • Author(s): Fujii H, Fujiwara H, Horie A, Sato Y, Konishi I
  • Journal Title: Hum Reprod Volume: 26 Pages: 299-306
  • Peer Reviewed
• [Journal Article] Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure (2011)
  • Author(s): Okitsu O, Kiyokawa M, Oda T, Miyake K, Sato Y, Fujiwara H
  • Journal Title: J Reprod Immunol Volume: 92 Pages: 82-7
  • Peer Reviewed
• [Journal Article] Management of retained products of conception with marked vascularity (2011)
  • Author(s): Kitahara T, Sato Y, Kakui K, Tatsumi K, Fujiwara H, Konishi I
  • Journal Title: J Gynecol Obstet Res Volume: 37 Pages: 458-64
  • NAID: 120005601063
  • Peer Reviewed
• [Journal Article] A case of successful recovery from delayed amniotic fluid embolism with prolonged cardiac resuscitation (2011)
  • Author(s): Hosono K, Matsumura N, Matsuda N, Fujiwara H, Sato Y, Konishi I
  • Journal Title: J Gynecol Obstet Res Volume: 37 Pages: 1122-5
  • Peer Reviewed
• [Journal Article] Prenatal treatment of meconium peritonitis with urinary trypsine inhibitor (2011)
  • Author(s): Izumi Y, Sato Y, Kakui K, Tatsumi K, Fujiwara H, Konishi I
  • Journal Title: Ultrasound Obstet Gynecol Volume: 37 Pages: 366-8
  • NAID: 120005601060
  • Peer Reviewed
• [Journal Article] Prenatal diagnosis of anterior sacral meningocele (2011)
  • Author(s): Sumi A, Sato Y, Kakui K, Tatsumi K, Fujiwara H, Konishi I
  • Journal Title: Ultrasound Obstet Gynecol Volume: 37 Pages: 493-6
  • NAID: 120005601061
  • Peer Reviewed
• [Journal Article] Prenatal findings in congenital leukemia : a case report (2011)
  • Author(s): Sato Y, Izumi Y, Minegishi K, Komada M, Yamada S, Kakui K, Tatsumi K, Mikami Y, Fujiwara H, Konishi I
  • Journal Title: Fetal Diagn Ther Volume: 29 Pages: 325-30
  • NAID: 120005601064
  • Peer Reviewed
• [Journal Article] EphrinA1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells (2011)
  • Author(s): Fujii H, Fujiwara H, Horie A, SuginamiK, Sato Y, Konishi I.
  • Journal Title: Hum Reprod Volume: 26(5) Issue: 5 Pages: 1163-70
  • DOI: 10.1093/humrep/der034
  • Peer Reviewed
• [Presentation] 骨盤腔の開放と後腹膜腔の展開を再考する-生殖機能の再建を目指して (2014)
  • Author(s): 藤原 浩
  • Organizer: 京都産婦人科医会期末特別講演会
  • Place of Presentation: 京都
  • Year and Date: 2014-03-29
• [Presentation] ヒト胎盤形成機構 -妊娠初期に何が起こっているのか (2014)
  • Author(s): 藤原 浩
  • Organizer: 石川県第3回周産期医療研修会
  • Place of Presentation: 金沢
  • Year and Date: 2014-01-16
• [Presentation] 骨盤腹膜の展開を再考する -受精と着床の場(胚のオアシス)の再建を目指して (2014)
  • Author(s): 藤原 浩
  • Organizer: 第149回和歌山市産婦人科部会研修
  • Place of Presentation: 和歌山
  • Year and Date: 2014-01-11
• [Presentation] シンポジウム8 Modern ART 不成功例不妊カップルに対するトータルケア 「着床障害への対応」 (2013)
  • Author(s): 藤原 浩
  • Organizer: 第58回日本生殖医学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2013-11-16
• [Presentation] 「生殖医療 : ベットサイド, ベンチサイド」 基礎から臨床への応用-内分泌, 免疫, 神経系ネットワークによる胚着床誘導機構 (2013)
  • Author(s): 藤原 浩
  • Organizer: 関東連合産科婦人科学会総会, 学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2013-10-27
• [Presentation] 骨盤後腹膜腔の開放を再考する-受精と着床の場 (オアシス) の機能再建 (2013)
  • Author(s): 藤原 浩
  • Organizer: 埼玉県産婦人科医会手術, 感染症研究会
  • Place of Presentation: 浦和
  • Year and Date: 2013-09-21
• [Presentation] 母体による胚の認識機構-胚の寄生と感染症は表裏一体か (2013)
  • Author(s): 藤原 浩
  • Organizer: 京都, 金沢STIエキスパートミーティング
  • Place of Presentation: 金沢
  • Year and Date: 2013-06-28
• [Presentation] 乳癌患者の卵巣機能に関する諸問題 (2013)
  • Author(s): 藤原 浩
  • Organizer: 第41回北陸産科婦人科学会学術講演会
  • Place of Presentation: 新潟
  • Year and Date: 2013-06-08
• [Presentation] 着床をめぐるトピックス (2013)
  • Author(s): 藤原 浩
  • Organizer: ナースのための ART医学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2013-05-26
• [Presentation] クリニカルカンファレンス2(生殖) 難治性不妊と治療 1)生理学的見地から (2013)
  • Author(s): 藤原 浩
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
  • Year and Date: 2013-05-10
• [Presentation] Eph-ephrin A system is a new candidate to regulate choriocarcinoma invasion (2013)
  • Author(s): Fujiwara H, Nishioka Y, Matsumoto H, Suginami K, Horie A, Tani H, Matsumura N, Baba T, Sato Y, Araki Y, Konishi I
  • Organizer: IGCS Regional Meeting on Gynecologic Cancers
  • Place of Presentation: Bali Indonesia
• [Presentation] シンポジウム８Modern ART 不成功例不妊カップルに対するトータルケア 着床障害への対応 (2013)
  • Author(s): 藤原 浩
  • Organizer: 第58回日本生殖医学会学術講演会
  • Place of Presentation: 兵庫県神戸市 神戸国際会議場
  • Invited
• [Presentation] ワークショップ２ 「生殖医療：ベットサイド・ベンチサイド」 基礎から臨床への応用 -内分泌・免疫・神経系ネットワークによる胚着床誘導機構- (2013)
  • Author(s): 藤原 浩
  • Organizer: 関東連合産科婦人科学会総会・学術集会
  • Place of Presentation: 静岡県浜松市 アクトシティ浜松
  • Invited
• [Presentation] クリニカルカンファレンス２（生殖） 難治性不妊と治療 １）生理学的見地から (2013)
  • Author(s): 藤原 浩
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 北海道札幌市 ロイトン札幌
  • Invited
• [Presentation] 母体による胚認識機構 (2012)
  • Author(s): 藤原 浩
  • Organizer: 平成 24年度 日本家畜臨床感染症研究会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-07
• [Presentation] ART基礎シリーズ講義(3) 「初期発生から着床」 (2012)
  • Author(s): 藤原 浩
  • Organizer: 第30回日本受精着床学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2012-08-30
• [Presentation] Intrauterine administration of autologous peripheral blood mononuclear cells improves implantation rates (2012)
  • Author(s): Fujiwara H
  • Organizer: 4th Japan-Korea ART conference 2012
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2012-03-23
  • Invited
• [Presentation] シンポジウム「胚の死滅による妊娠喪失」 「自己免疫細胞を用いた不妊治療 -着床期胚の生存を高める試み-」 (2012)
  • Author(s): 藤原 浩
  • Organizer: 平成 23年度 日本獣医師会獣医学術学会年次大会
  • Place of Presentation: 札幌
  • Year and Date: 2012-02-03
• [Presentation] 母体循環系の細胞成分を介した新しい胚の着床誘導機構 (2012)
  • Author(s): 藤原 浩
  • Organizer: 第11回東海不妊内分泌研究会
  • Place of Presentation: 静岡
  • Year and Date: 2012-01-28
• [Presentation] 教育講演「ヒト胚着床機構の概要と新しい知見」 (2012)
  • Author(s): 藤原 浩
  • Organizer: 第17回日本臨床エンブリオロジスト学会ワークショップ, 学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2012-01-08
• [Presentation] 免疫細胞による着床誘導機構 (2011)
  • Author(s): 藤原 浩
  • Organizer: 第56回日本生殖医学会学術講演会 シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-08
• [Presentation] Novel local regulatory mechanisms for human embryo attachment and invasion (2011)
  • Author(s): Fujiwara H
  • Organizer: The 4th International Conference of Repeated Implantation Failure
  • Place of Presentation: Guangzhou, China
  • Year and Date: 2011-11-12
• [Presentation] Novel local regulatory mechanisms for human embryo attachment and invasion (2011)
  • Author(s): Fujiwara H
  • Organizer: 4th International Conference of Repeated Implan tation Failure
  • Place of Presentation: 広州中国
  • Year and Date: 2011-11-12
• [Presentation] 着床不全の基礎と臨床 (2011)
  • Author(s): 藤原 浩
  • Organizer: 第125回近畿産科婦人科学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-06
• [Presentation] 内分泌-免疫系を介した胚シグナルによる着床誘導機構 (2011)
  • Author(s): 藤原 浩
  • Organizer: 第104回日本繁殖生物学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2011-09-14
• [Presentation] Improvement of implantation rates using autologous peripheral blood mononuclear cells (2011)
  • Author(s): Fujiwara H
  • Organizer: 16th World Congress on In Vitro Fertilization
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2011-09-12
  • Invited
• [Presentation] Improvement of implantation rates using autologous peripher al blood mononuclear cells (2011)
  • Author(s): Fujiwara H
  • Organizer: 16th World Congress on In Vitro Fertilization
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2011-09-12
• [Presentation] Circulating immune cells can promote embryo implantation (2011)
  • Author(s): Fujiwara H
  • Organizer: 31th Annual Meeting of The American Society for Reproductive Immunology
  • Place of Presentation: Salt Lake City, U.S.A
  • Year and Date: 2011-05-20
  • Invited
• [Presentation] Circulating immune cells can promote embryo implantation (2011)
  • Author(s): Fujiwara H
  • Organizer: 31th Annual Meeting of The American Society for Reproductive Immunology
  • Place of Presentation: Salt Lake City, U.S.A.
  • Year and Date: 2011-05-20
• [Book] 'Immune regulation of human embryo implantation by circulating blood cells' The Human Embryo Ed. Yamada S (2012)
  • Author(s): Fujiwara H, Sato Y, Ideta A, Aoyagi Y, Araki Y, Imakawa K
  • Publisher: In Tech
• [Book] Immune regulation of human embryo implantation by circulating blood cells (2012)
  • Author(s): Fujiwara H
  • Total Pages: 12
  • Publisher: InTech Open Access Publisher
• [Book] 「卵子学」森 崇英 編 (2011)
  • Author(s): 藤原 浩
  • Publisher: 京都大学学術出版会