Research on fertility improvement using cyclodextrins

• Project/Area Number: 26860039
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Takeo Toru 熊本大学, 生命資源研究・支援センター, 講師 (10517014)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 不妊 / シクロデキストリン / 精子 / 受精能獲得 / コレステロール / リン脂質 / 生体膜 / 体外受精 / 環状オリゴ糖 / 脂質 / 超活性化 / 不妊治療薬 / 受精 / 生体膜脂質 / リピッドラフト / 低受精能 / 不妊治療

Outline of Final Research Achievements

The number of subfertile and infertile patients is increasing in advanced countries. However, there is no innovative solution to improve their fertility. In this study, we examined the effect of cyclodextrins on the functions of mouse sperm. Methyl-beta-cyclodextrin enhanced fertility and promoted acrosome reaction and hyperactivation by enhancing membrane fluidity with the reduction of cholesterol in sperm membrane. Dimethyl-alpha-cyclodextrin also increased fertility of sperm by induction of lipids efflux from sperm membrane. These results suggest that cyclodextrins is applicable as fertility activator in the in vitro fertilization.

Research Products

• [Journal Article] Fertility of cold-stored mouse sperm is recovered by promoting acrosome reaction and hyperactivation after cholesterol efflux by methyl-β-cyclodextrin (2017)
  • Author(s): Hidetaka Yoshimoto, Toru Takeo, Tetsumi Irie, Naomi Nakagata
  • Journal Title: Biology of Reproduction Volume: 96 Issue: 2 Pages: 446-455
  • DOI: 10.1095/biolreprod.116.142901
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cysteine analogs with a free thiol group promote fertilization by reducing disulfide bonds in the Zona Pellucida of mice (2015)
  • Author(s): Takeo, T., Horikoshi, Y., Nakao, S., Sakoh, K., Ishizuka, Y., Tsutsumi, A., Fukumoto, K., Kondo, T., Haruguchi, Y., Takeshita, Y., Nakamuta, Y., Tsuchiyama, S. and Nakagata, N.
  • Journal Title: Biol. Reprod. Volume: 92(4)90 Issue: 4 Pages: 1-7
  • DOI: 10.1095/biolreprod.114.125443
  • Peer Reviewed / Open Access
• [Journal Article] Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C57BL/6 Female Mice (2015)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: 1-11
  • DOI: 10.1371/journal.pone.0128330
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Application of Cryotechnology to Establish Efficient Research Infrastructure for Genetically Engineered Mice (2015)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Journal Title: Cryobiology and Cryotechnology Volume: 61 Pages: 19-26
  • Peer Reviewed
• [Journal Article] El metodo CARD se consolida como el mejor protocolo de tecnologia de la reproduccion de raton (2015)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Journal Title: Animales De Laboratorio Volume: 65 Pages: 17-22
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 受精促進作用を示す環状オリゴ糖を用いた新規不妊治療法の開発 (2017)
  • Author(s): 竹本賢司，中尾聡宏, 吉本英高、入江徹美、竹尾 透、中潟直己
  • Organizer: 日本薬学会第137年会 2017年3月26日
  • Place of Presentation: 東北大学
• [Presentation] Efficient production of mouse oocytes using superovulation by immunization against inhibin (2016)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Organizer: 13th Transgenic Technology Meeting
  • Place of Presentation: Clarion Congress Hotel Prague
  • Year and Date: 2016-03-20
  • Int'l Joint Research / Invited
• [Presentation] シクロデキストリン誘導性受精能獲得効果を利用した新規不妊治療の開発 (2016)
  • Author(s): 竹本賢司、中尾聡宏、吉本英高、入江徹美、竹尾 透、中潟直己
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 最新の生殖工学技術を用いたマウス研究の迅速化 (2016)
  • Author(s): 竹尾 透、吉本英高、椋木歩、竹本賢司、白角一樹、田村香菜、野田雅文、須賀原千明、桐木平小春、山下紀代子、近藤朋子、春口幸恵、中牟田裕子、竹下由美、梅野智子、石田恵理、高橋郁、岩本まり、土山修治、坂本亘、中川佳子、中潟直己
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] シクロデキストリンによる受精能獲得過程における生体膜脂質環境の変化 (2016)
  • Author(s): 竹本賢司，中尾聡宏, 吉本英高、竹尾 透、中潟直己
  • Organizer: 第109回日本繁殖生物学会
  • Place of Presentation: 麻布大学
• [Presentation] The amount of membrane cholesterol determines the cryotolerance of sperm among mouse strains (2016)
  • Author(s): Masafumi Noda, Yumiko Hirose, Yuta Ishizuka, Toru Takeo, Naomi Nakagata
  • Organizer: 7th AFLAS Congress
  • Place of Presentation: ラッフルズ国際会議場
  • Int'l Joint Research
• [Presentation] マウス冷蔵精子の超活性化がメチル-β-シクロデキストリンによって誘起される (2016)
  • Author(s): 吉本英高、桐木平小春、竹尾 透、入江徹美、中潟直己
  • Organizer: 第7回シクロデキストリンワークショップ
  • Place of Presentation: 熊本大学
• [Presentation] Effect of cholesterol efflux from plasma membrane on the fertility of cold-stored mouse sperm (2016)
  • Author(s): Hidetaka Yoshimoto, Shiori Takeuji, Yumiko Hirose, Toru Takeo and Naomi Nakagata
  • Organizer: The 2016 AMMRA & AMPC meeting
  • Place of Presentation: Hakone-Yumoto Hot Spring Hotel Okada
  • Int'l Joint Research
• [Presentation] マウス冷蔵精子における生体膜中コレステロール量の変化が受精能に及ぼす影響 (2016)
  • Author(s): 吉本英高、武氏志保里、廣瀬優美子、竹尾 透、中潟直己
  • Organizer: 第63回日本実験動物学会
  • Place of Presentation: ミューザ川崎シンフォニーホール
• [Presentation] 環状オリゴ糖による生体膜脂質環境の変化が精子の受精能を向上させる (2015)
  • Author(s): 中尾 聡宏,、酒匂 一仁、竹本 賢司、吉本 英高、堀越 裕佳、石束 祐太、竹尾 透、中潟 直己
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Efficient production of genetically engineered mice by ultra-superovulation using inhibin antiserum (2015)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Organizer: The 2nd Oceania Transgenic/Cryopreservation Symposium
  • Place of Presentation: University of Tasmania’s Medical Sciences Precinct
  • Year and Date: 2015-11-18
  • Int'l Joint Research / Invited
• [Presentation] CARD Revolution in Mouse Reproductive Technology (2015)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Organizer: Shanghai Laboratory Animal Science
  • Place of Presentation: 上海交通大学医学部
  • Year and Date: 2015-08-13
  • Int'l Joint Research / Invited
• [Presentation] 生殖工学技術を用いた遺伝子改変マウスの兵站術 (2015)
  • Author(s): 竹尾 透
  • Organizer: 第8回トランスポーター研究会九州支部会
  • Place of Presentation: 鹿児島大学医学部
  • Year and Date: 2015-07-18
  • Invited
• [Presentation] 精子生体膜脂質の漏出による精子受精能への影響 (2015)
  • Author(s): 中尾聡宏 、竹本賢司、竹尾 透、笹岡俊邦、中潟直己
  • Organizer: 平成27年度日本生化学会関東支部例会
  • Place of Presentation: 新潟日報メディアシップ
  • Year and Date: 2015-06-20
• [Presentation] Improving the efficiency of mouse reproductive technology for connecting the world (2015)
  • Author(s): Toru Takeo and Naomi Nakagata
  • Organizer: 8th Workshop on Innovative Mouse Models
  • Place of Presentation: Leiden University Medical Center (LUMC)
  • Year and Date: 2015-06-11
  • Int'l Joint Research / Invited
• [Presentation] Mechanisms of sperm activation by various cyclodextrins in mice (2015)
  • Author(s): Yuka Horikoshi, Kenji Takemoto, Satohiro Nakao, Kazuhito Sakoh, Toru Takeo, Naomi Nakagata
  • Organizer: 8th Asian Cyclodextrin Conference
  • Place of Presentation: 熊本県民交流会パレア
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Methyl-β-cyclodextrin recovered the fertilizing ability of the cold-stored mouse sperm (2015)
  • Author(s): Hidetaka Yoshimoto, Shiori Takeuji, Toru Takeo, Naomi Nakagata
  • Organizer: 8th Asian Cyclodextrin Conference
  • Place of Presentation: 熊本県民交流会パレア
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] 環状オリゴ糖による精子の活性化機構の解明 (2015)
  • Author(s): 竹尾 透、 中尾 聡宏、 酒匂 一仁、 堀越 裕佳、 中潟 直己
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸サンボーホールエリア（兵庫県）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 生殖機能改善薬としてのシクロデキストリンの可能性 (2014)
  • Author(s): 中尾 聡宏、竹尾 透、中潟 直己
  • Organizer: 第31回日本薬学会九州支部大会
  • Place of Presentation: 第一薬科大学（福岡県）
  • Year and Date: 2014-12-06 – 2014-12-07
• [Presentation] 生殖工学と薬学の融合が拓く世界 (2014)
  • Author(s): 竹尾 透
  • Organizer: 第8回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 熊本大学薬学部（熊本県）
  • Year and Date: 2014-11-15 – 2014-11-16
  • Invited
• [Presentation] 生殖細胞の低温保存技術を利用した遺伝子改変マウス研究基盤の構築 (2014)
  • Author(s): 竹尾 透、中潟 直己
  • Organizer: 第59回低温生物工学会大会及びセミナー
  • Place of Presentation: 九州大学国際ホール（福岡県）
  • Year and Date: 2014-06-28
  • Invited
• [Presentation] 生体膜脂質の漏出がマウス精子の受精能に及ぼす影響 (2014)
  • Author(s): 竹尾 透、酒匂 一仁、中尾 聡宏、石束 祐太、吉本 英高、堀越 裕佳、鹿瀬 優美子、武氏 志保里、椋木 歩、中潟 直己
  • Organizer: 第６１回日本実験動物学会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2014-05-15 – 2014-05-17
• [Remarks] 熊本大学 生命資源研究・支援センター 資源開発分野
  • URL: http://irda.kuma-u.jp/divisions/reproductive_engineer/reproductive_engineer.html
• [Remarks] 竹尾 透: Research Map
  • URL: http://researchmap.jp/read0126236
• [Remarks] Nakagata Lab
  • URL: http://nakagata-lab.weebly.com/
• [Remarks] 生命資源研究・支援センター 資源開発分野
  • URL: http://irda.kuma-u.jp/divisions/reproductive_engineer/reproductive_engineer.html
• [Remarks] 熊本大学CARDマウスバンクシステム
  • URL: http://card.medic.kumamoto-u.ac.jp/card/japanese/mousebank/