Translational research aiming at drug development to enhance sperm motility, and to improve the fertility rate.

• Project/Area Number: 24659726
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUGIHARA Kazuhiro 浜松医科大学, 医学部, 准教授 (00265878)
• Co-Investigator(Kenkyū-buntansha): KANAYAMA Naohiro 浜松医科大学, 医学部, 教授 (70204550)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 生殖医学 / トランスレーショナル・リサーチ

Outline of Final Research Achievements

GWRQ enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ enhanced both progressive motility and rapid motility in wild type mouse sperm.
FGF and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with EBG, which specifically polyLacs, enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells.

Research Products

• [Journal Article] Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. (2014)
  • Author(s): Sugihara K, Kobayashi Y, Suzuki A, Tamura N, Motamedchaboki K, Huang C-T, Akama TO, Pecotte J, Frost P, Bauer C, Jimenez JB, Nakayama J, Aoki D, Fukuda MN
  • Journal Title: Nature communications Volume: 22;5:4478 Pages: 1-9
  • Peer Reviewed / Open Access
• [Journal Article] A Comparison between Placental Gene Expression of 11βHydroxysteroid Dehydrogenases and Infantile Growth during at Ten Months. (2014)
  • Author(s): Muramatsu-Kato K, Itoh, H, Kohmura Y, Murakami H, Uchida T, Suzuki K, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re. Volume: - Issue: 2 Pages: 465-472
  • DOI: 10.1111/jog.12200
  • Peer Reviewed
• [Journal Article] C1 esterase inhibitor activity in amniotic fluid embolism. (2014)
  • Author(s): Tamura N. Kimura S, Farhana M, Uchida T, Suzuki K, Sugihara K, Itoh H, Ikeda T, Kanayama N
  • Journal Title: Critical Care Medicine. Volume: -
  • Peer Reviewed
• [Journal Article] Zinc Coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation. (2013)
  • Author(s): Ozawa H, Asahina T, Murakami H, Yaguchi C, Kohmura Y, Kohno E, Hirano T, Horiuchi K, Tamura N, Sugihara K, Ooi H, Kanayama N
  • Journal Title: Fetal Digan Ther. Volume: 33(2) Pages: 90-97
  • Peer Reviewed
• [Journal Article] Cerebral oxygen saturation evaluated by near-infrared timeresolved spectroscopy (TRS) in pregnant women duringcesarean section -A promising new method of maternal monitoring - (2013)
  • Author(s): Yamazaki K, Suzuki K, Itoh H, Muaramatsu K, Nagahashi K, Tamura N, Uchida T, Sugihara K, Maeda H, Kanayama N
  • Journal Title: Clin Physiol Funct I. Volume: 33(2) Pages: 109-116
  • Peer Reviewed
• [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero. (2013)
  • Author(s): Kohmura YK, Kanayama N, Muramatsu K, Tamura N, Yaguchi C, Uchida T, Suzuki K, Sugihara K, Aoe S, Sasaki T, Suganami T, Ogawa Y, Itoh H
  • Journal Title: Reprod Sci. Volume: 20(7) Pages: 813-827
  • Peer Reviewed
• [Journal Article] Regulation of steroid hormones by HNK-1 Chst10 in vivo in the mouse. (2013)
  • Author(s): Suzuki-Anekoji M, Suzuki A, Wu SW, Angata K, Murai KK, Sugihara K, Akama TO, Khoo KH, Nakayama J, Fukuda MN, Fukuda M
  • Journal Title: J Biol Chem. Volume: 288(7) Pages: 5007-5016
  • Peer Reviewed
• [Journal Article] Changes of maternal dietary intake, body weight and fetal growth through pregnancy in pregnant Japanese women. (2013)
  • Author(s): Kubota K, Itoh H, Tasaka M, Naito H, Fukuoka Y, Muramatsu K, Kohmura KY, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re. Volume: 39(9) Pages: 1383-1390
  • Peer Reviewed
• [Journal Article] Tumor targeting by a carbohydrate ligand-mimicking Peptide. (2013)
  • Author(s): Hatakeyama S, Shibata TK, Tobisawa Y, Ohyama C, Sugihara K, Fukuda MN
  • Journal Title: Methods in Molecular Biology. Volume: 1022 Pages: 369-386
  • Peer Reviewed
• [Journal Article] Regulation of human sperm motility by polylactosamines derived from seminal fluid. (2013)
  • Author(s): Sugihara K, Shibata TK, Takata K, Kimura T, Kanayama N, Williams R, Hatakeyama S, Akama TO, Kuo CW, Khoo KH, Fukuda MN
  • Journal Title: FEBS Lett. Volume: 587 Pages: 3195-3201
  • Peer Reviewed
• [Journal Article] Zinc coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation. (2012)
  • Author(s): Ozawa H, Asahina T, Murakami H, Yaguchi C, Kohmura Y, Kohno E, Hirano T, Horiuchi K, Tamura N, Sugihara K, Ooi H, Kanayama N.
  • Journal Title: Fetal Diagn Ther. Volume: 33(2) Pages: 90-97
  • Peer Reviewed
• [Journal Article] Trophinin in cell adhesion and signal transduction. (2012)
  • Author(s): Fukuda MN, Sugihara K.
  • Journal Title: Front Biosci (Elite Ed). Volume: 1;4 Pages: 342-350
  • Peer Reviewed
• [Journal Article] Cell adhesion molecules in human embryo implantation. (2012)
  • Author(s): Fukuda MN, Sugihara K.
  • Journal Title: Sheng Li Xue Bao. Volume: 64(3) Pages: 247-258
  • Peer Reviewed
• [Journal Article] Carbohydrate mimetic peptides as research reagent and therapeutic. (2012)
  • Author(s): Fukuda MN, Hatakeyama S, Sugihara K.
  • Journal Title: Biol Pharm Bull. Volume: 35(10) Pages: 1626-1632
  • NAID: 130001872369
  • Peer Reviewed
• [Journal Article] Enhancement of mouse sperm motility by trophinin-binding peptide. (2012)
  • Author(s): Park SK, Yoon J, Wang L, Shibata TK, Motamedchaboki K, Shim KJ, Chang MS, Lee SH, Tamura N, Hatakeyama S, Nadano D, Sugihara K, Fukuda MN.
  • Journal Title: Reprod Biol Endocrinol. Volume: 10 Pages: 105-105
  • Peer Reviewed
• [Journal Article] In vivo regulation of steroid hormones by the Chst10 sulfotransferase in mouse. (2012)
  • Author(s): Suzuki-Anekoji M, Suzuki A, Wu SW, Angata K, Murai KK, Sugihara K, Akama TO, Khoo KH, Nakayama J, Fukuda MN, Fukuda M.
  • Journal Title: J Biol Chem. Volume: 288(7) Pages: 5007-5016
  • Peer Reviewed
• [Journal Article] Successful living donor liver transplantation for fulminant hepatic failure that manifested immediately after cesarean delivery. (2012)
  • Author(s): Horikoshi Y, Itoh H, Kikuchi S, Uchida T, Suzuki K, Sugihara K, Kanayama N, Mori A, Uemoto S.
  • Journal Title: ASAIO J. Volume: 58(2) Pages: 174-176
  • Peer Reviewed
• [Journal Article] Transient ligation of umbilical vessels elevates placental tissue oxygen index (TOI) values measured by near-infrared spectroscopy (NIRS) in clawn miniature pig animal model. (2012)
  • Author(s): Suzukin K, Itoh H, Muramatsu K, Yamazaki K, Nagahashi K, Furuta N, Tamura N, Uchida T, Sugihara K, Sumimoto K, Kanayama N.
  • Journal Title: Clin Exp Obstet Gynecol. Volume: 39(3) Pages: 293-298
  • Peer Reviewed
• [Journal Article] Association Between Body Weight at Weaning and Remodeling in the Subcutaneous Adipose Tissue of Obese Adult Mice With Undernourishment In Utero. (2012)
  • Author(s): Kohmura YK, Kanayama N, Muramatsu K, Tamura N, Yaguchi C, Uchida T, Suzuki K, Sugihara K, Aoe S, Sasaki T, Suganami T, Ogawa Y, Itoh H.
  • Journal Title: Reprod Sci. Volume: 20(7) Pages: 813-827
  • Peer Reviewed
• [Journal Article] Cerebral oxygen saturation evaluated by near-infrared time-resolved spectroscopy (TRS) in pregnant women during caesarean section - a promising new method of maternal monitoring. (2012)
  • Author(s): Yamazaki K, Suzuki K, Itoh H, Muramatsu K, Nagahashi K, Tamura N, Uchida T, Sugihara K, Maeda H, Kanayama N.
  • Journal Title: Clin Physiol Funct Imaging. Volume: 33(2) Pages: 109-116
  • Peer Reviewed
• [Presentation] Attenuation of fibroblast growth factor signaling by poly- N- acatyllactosamine type glycans implicated to human sperm motility. (2015)
  • Author(s): Shibata T, Sugihara K, Kanayama N
  • Organizer: 62nd Annual Meeting of the Society for Reproductive Investigation (SRI).
  • Place of Presentation: San Francisco, California. USA
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 精液へ分泌される糖鎖ポリラクトサミンによる精子運動の調節機構 (2014)
  • Author(s): 柴田俊章，杉原一廣，田村直顕，金山尚裕
  • Organizer: 第59回日本生殖医学会学術講演会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2014-12-04 – 2014-12-05
• [Presentation] 精液へ分泌される糖鎖ポリラクトサミンによる精子運動の調節機構 (2014)
  • Author(s): 柴田俊章，杉原一廣，髙田佳世子，中村友紀，伊東宏晃，金山尚裕
  • Organizer: 日本産科婦人科学会第66回学術講演会
  • Place of Presentation: 東京国際フォーラム、東京
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] 臨床的羊水塞栓症における C1 インヒビター活性の検討 (2013)
  • Author(s): 田村直顕、木村 聡、杉原 一廣、伊東 宏晃、池田 智明、金山 尚裕
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: ロイトン札幌他、北海道
• [Presentation] Identification of sulfated N-acetyl-lactosaminyl oligosaccharide structures as epitopes recognized by humanized monoclonal antibody HMOCC-1 raised against ovarian cancer (2013)
  • Author(s): ShibataTK, Sugihara K, Fukuda MN, Suzuki A, Kanayama N, Aoki D
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: ロイトン札幌他、北海道
• [Presentation] 精液へ分泌される糖鎖ポリラクトサミンによる精子運動の調節機構 (2013)
  • Author(s): 柴田俊章、杉原一廣、木村たか子、高田佳世子、中村友紀、俵史子、金山尚裕
  • Organizer: 第31回日本受精着床学会総会・学術講演会
  • Place of Presentation: 別府国際コンベンションセンター、大分
• [Presentation] 糖鎖をmimicするペプチドを用い腫瘍血管内皮細胞を標的とするドラッグデリバリーシステム (2013)
  • Author(s): 杉原一廣
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台国際センター、東北大学百周年記念会館川内萩ホール、宮城
• [Presentation] 子宮内膜症に対するペプチド治療薬 (2013)
  • Author(s): 杉原一廣
  • Organizer: BioJapan 2013 World Business Forum
  • Place of Presentation: パシフィコ横浜、神奈川
• [Presentation] 腫瘍血管表面特異マーカーアネキシン１を標的とするIF7を用いた抗腫瘍薬 (2013)
  • Author(s): 杉原一廣
  • Organizer: BioJapan 2013 World Business Forum
  • Place of Presentation: パシフィコ横浜、神奈川
  • Invited
• [Presentation] ペプチド創薬 (2013)
  • Author(s): 杉原一廣
  • Organizer: 第5回 Japan Endometriosis Forum
  • Place of Presentation: ハイアットリージェンシー大阪、大阪
  • Invited
• [Presentation] Targeted drug delivery to brain tumor vasculature by carbohydrate mimetic peptide in mouse glioma model. (2013)
  • Author(s): Misa Suzuki‐Anekoji, Jiunn‐Chern Yeh, Motohiro Nonaka, Toshiaki K. Shibata, Jun Nakayama, Tomoya O. Akama, Kazuhiro Sugihara, Minoru Fukuda, Michiko N. Fukuda
  • Organizer: The 2013 Annual Conference of the Society for Glycobiology
  • Place of Presentation: St.Petersburg Florida, USA
• [Presentation] Attenuation of fibroblast growth factor signaling by poly-N-acatyllactosamine type glycans implicated to human sperm motility. (2013)
  • Author(s): Sugihara K, Shibata TK, Akama TO, Kuo C-W, Khoo K-H, Fukuda MN
  • Organizer: The 2013 Annual Conference of the Society for Glycobiology
  • Place of Presentation: St.Petersburg Florida, USA
• [Presentation] Targeted drug delivery to tumor vasculature by the IF7 peptide in mouse glioma model. (2012)
  • Author(s): Misa Suzuki-Anekoji, Toshiaki K. Shibata, Jun Nakayama, Tomoya O. Akama, Kazuhiro Sugihara, Minoru Fukuda and Michiko N. Fukuda
  • Organizer: Joint meeting of the Society for Glycobiology and the American Society for Matrix Biology.
  • Place of Presentation: San Diego, CA. USA
• [Presentation] 糖鎖を模倣するペプチド“IF7”による腫瘍血管を標的とする癌治療薬 (2012)
  • Author(s): 杉原一廣
  • Organizer: BioJapan 2012. World Business Forum.
  • Place of Presentation: Pacifico Yokohama, 横浜、神奈川
• [Presentation] 糖鎖をmimicするペプチドを用い腫瘍血管内皮細胞を標的とするドラッグデリバリーシステム (2012)
  • Author(s): 杉原一廣
  • Organizer: 第16回日本がん分子標的治療学会学術集会
  • Place of Presentation: 西日本総合展示場, 北九州, 福岡
• [Presentation] 糖鎖をmimicするペプチドを用い腫瘍血管内皮細胞を標的とするドラッグデリバリーシステム (2012)
  • Author(s): 杉原一廣
  • Organizer: 2012年独立行政法人産業技術総合研究所・糖鎖医工学研究センターセミナー
  • Place of Presentation: つくば, 茨城
  • Invited
• [Presentation] 糖鎖をmimicするペプチド「IF7」による腫瘍血管を標的とする癌治療と診断 (2012)
  • Author(s): 杉原一廣
  • Organizer: 第42回 Medical Photonics Seminar
  • Place of Presentation: 浜松, 静岡
  • Invited
• [Presentation] 精子運動の活性化と受精率・胚発育率の向上を目指したトランスレーショナル・リサーチ (2012)
  • Author(s): 杉原一廣，髙田佳世子，柴田俊章，伊東宏晃，金山尚裕
  • Organizer: 第64回日本産科婦人科学会
  • Place of Presentation: 神戸ポートピアホテル, 神戸
• [Presentation] 糖鎖をmimicするペプチドIF7を用い腫瘍血管内皮細胞を標的とするドラッグデリバリーシステム (2012)
  • Author(s): 杉原一廣、畠山真吾、柴田俊章、福田道子
  • Organizer: 第28回日本DDS学会
  • Place of Presentation: 札幌コンベンションセンター, 札幌, 北海道
• [Presentation] ヒト型モノクローナル抗体HMOCC-1により特異的に認識されるモノまたはジ硫酸化N-アセチルラクトサミンオリゴ糖構造の同定 (2012)
  • Author(s): 柴田俊章、杉原一廣、福田道子、鈴木淳、鈴木直、金山尚裕、青木大輔
  • Organizer: 婦人科がん分子標的研究会学術集会
  • Place of Presentation: 日光市, 栃木県
• [Presentation] ヒト型モノクローナル抗体HMOCC-1により特異的に認識されるオリゴ糖構造の同定 (2012)
  • Author(s): 柴田俊章、杉原一廣、福田道子、鈴木淳、鈴木直、金山尚裕、青木大輔
  • Organizer: 第50回癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜, 横浜, 神奈川
• [Book] Handbook of Glycosyltransferases and Related Genes. (2014)
  • Author(s): FukudaMN, Sugihara K, Akama TO
  • Total Pages: 10
  • Publisher: SpringerReference.
• [Book] 泌尿器外科 (2013)
  • Author(s): 畠山真吾、柴田俊章、田村直顕、飛澤悠葵、米山徹、杉原一廣、大山力、福田道子
  • Total Pages: 4
  • Publisher: 医学図書出版
• [Book] Molecular Biology Research Materials. (2012)
  • Author(s): Shingo Hatakeyama, Toshiaki K. Shibata, Yuki Tobisawa, Chikara Ohyama, Kazuhiro Sugihara, and Michiko N. Fukuda
  • Publisher: Humana Press, Inc.
• [Book] 産婦人科の実際 (2012)
  • Author(s): 杉原一廣
  • Publisher: 金原出版
• [Remarks] 浜松医科大学 教員総覧 杉原一廣
  • URL: http://www.hama-med.ac.jp/uni_introduction_report_souran_07161504.html
• [Remarks] 浜松医科大学 教員総覧 杉原一廣
  • URL: http://www.hama-med.ac.jp/uni_introduction_report_souran_07161504.html
• [Remarks] 「バイオビジネスアワード」受賞について（知財活用推進本部）
  • URL: http://www.hama-med.ac.jp/uni_topics_20130225.html