Structural and functional analyses of reproduction-specific carbohydrate antigen recognized by an auto-antibody, Ts4

• Project/Area Number: 25462575
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Juntendo University
• Principal Investigator: Araki Yoshihiko 順天堂大学, 医学(系)研究科(研究院), 准教授 (70250933)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 抗精子抗体 / N-結合型糖鎖 / 受精 / 生殖細胞 / マウス / 抗精子自己抗体 / 先体反応 / TEX101 / バイセクト型糖鎖 / α-N-アセチルグルコサミニダーゼ / α-N-アセチルグルコサミダーゼ

Outline of Final Research Achievements

TEX101, a glycoprotein specific for germ cell, is an essential molecule in the process of reproduction. Previously, my research group showed that the N-linked oligosaccharide (OS) chain on testicular proteins including TEX101 is antigen-epitope for an anti-sperm auto monoclonal antibody, Ts4. Since the tissue distribution of the Ts4-recognized molecule is limited to reproductive related tissues, Ts4-epitope (OS chain) may have unique structure.
The main aim of this study was to clarify chemical structure of the Ts4-epitope. Using LS-MS and lectin binding analyses combined with glycohydrolases digestion, OS structure of the Ts4 epitope is determined as agalacto-biantennary N-glycan with bisecting GlcNAc carrying fucose residues. In addition, Ts4 has an inhibitory effect on the fertilization in vitro.
Taken together, the OS structure recognized by Ts4 is suggested to be an important physiological function(s) in the process of reproduction in mice model.

Research Products

• [Journal Article] Simple quantitation for potential serum disease biomarker peptides, primarily identified by a peptidomics approach in the serum with hypertensive disorders of pregnancy. (2016)
  • Author(s): Hamamura K, Nonaka D, Ishikawa H, Banzai M, Yanagida M, Nojima M, Yoshida K, Lee LJ, Tanaka K, Takamori K, Takeda S, Araki Y
  • Journal Title: Ann Clin Biochem Volume: 53 Issue: 1 Pages: 85-96
  • DOI: 10.1177/0004563215583697
  • Peer Reviewed
• [Journal Article] TEX101, a glycoprotein essential for sperm fertility, is required for stable expression of Ly6k on testicular germ cells (2016)
  • Author(s): Endo S, Yoshitake H, Tsukamoto H, Matsuura H, Kato K, Sakuraba M, Takamori K, Fujiwara H, Takeda S, Araki Y
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 23616-23616
  • DOI: 10.1038/srep23616
  • Peer Reviewed / Open Access
• [Journal Article] Identification of an anti-sperm auto-monoclonal antibody (Ts4)-recognized molecule in the mouse sperm acrosomal region and its inhibitory effects on fertilization in vitro. (2016)
  • Author(s): Yoshitake H., Oda R., Yanagida M., Kawasaki Y., Sakuraba M., Takamori K., Hasegawa A., Fujiwara H., Araki Y.
  • Journal Title: J.Reprod.Immunol. Volume: 115 Pages: 6-13
  • DOI: 10.1016/j.jri.2016.04.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulatory and pro-metastatic function of myeloid-derived suppressive cells requires education from tumor-associated B cells. (2015)
  • Author(s): Bodogai M., Moritoh K., Lee-Chang C., Hollander M.C., Sherman-Baust C., Wersto R., Araki Y., Miyoshi I., Yang L., Trinchieri G., Biragyn A.
  • Journal Title: Cancer Res. Volume: 75 Issue: 17 Pages: 3456-3465
  • DOI: 10.1158/0008-5472.can-14-3077
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Chemical characterization of N-linked oligosaccharide as the antigen epitope recognized by an anti-sperm auto-monoclonal antibody, Ts4. (2015)
  • Author(s): Yoshitake H, Hashii N, Kawasaki N, Endo S, Takamori K, Hasegawa A, Fujiwara H, Araki Y.
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0133784-e0133784
  • DOI: 10.1371/journal.pone.0133784
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] 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] Expression of TEX101, regulated by ACE, is essential for the production of fertile mouse spermatozoa (2013)
  • Author(s): FujiharaY, Tokuhiro K, Muro Y, Kondoh G, Araki Y, Ikawa M, Okabe M
  • Journal Title: PNAS Volume: 110(20) Issue: 20 Pages: 8111-6
  • DOI: 10.1073/pnas.1222166110
  • 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 Issue: 10 Pages: 141-148
  • DOI: 10.1111/jog.12140
  • Peer Reviewed
• [Presentation] Identification and confirmation of carbohydrate structure recognized by an anti-sperm monoclonal antibody Ts4, using lectin-binding and glycohydrolase-digestion assays. (2015)
  • Author(s): Yoshitake H., Hashii N., Kawasaki N., Oda R., Kawasaki Y., Sakuraba M., Endo S., Takamori K., Hasegawa A., Fujiwara H., Araki Y.
  • Organizer: The 30th Annual Meeting of the Japan Society for Immunology of Reproduction
  • Place of Presentation: 熊本市
  • Year and Date: 2015-11-21
• [Presentation] 雄性生殖細胞におけるTEX101/Ly6k複合体の分子安定性 (2015)
  • Author(s): 遠藤周一郎, 竹田 省, 荒木慶彦
  • Organizer: 第67回日本産婦人科学会学術講演会 ミニワークショップ（日本産科婦人科学会優秀演題賞・受賞）
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-09
• [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: The 2nd IGCS Regianal Meeting on Gynecologic Cancers
  • Place of Presentation: Bali, Indonesia.
• [Presentation] Structure of the oligosaccaride chain in the molecular epitope for anti-sperm auto-monoclonal antibody, Ts4. (2013)
  • Author(s): Yoshitake H, Endo S, Hasegawa A, Hashii N, Kawasaki N, Takamori K, Fujiwara H, Araki Y.
  • Organizer: Society for the Study of Reproduction, 46th Annual Meeting
  • Place of Presentation: Montreal, QC, Canada.
• [Book] 最先端バイオマーカーを用いた診断薬/診断装置開発と薬事対応 -妊娠高血圧症候群のバイオマーカーの探索・開発と診断薬 (2015)
  • Author(s): 荒木慶彦、濱村憲佑
  • Total Pages: 420
  • Publisher: 技術情報協会
• [Book] New Discoveries of Embryology -A novel concept of Fundus-Ovary-Salpinx-Para-Aorta implantation promoting unit during human embryo implantation. (2015)
  • Author(s): Fujiwara H, Araki Y, Saito S, Imakawa K, Kyo S, Shigeta M, Shiotani M, Horie A, Mori T.
  • Publisher: InTech Open Access Publisher
• [Remarks] Inst. for Environment. & Gender-Spec. Med.
  • URL: http://www.juntendo.ac.jp/english/department/gra/gender_specific_medicine/araki.html