Regulation of sperm capacitation through control of sperm membrane sterol levels by seminal vesicle secretory proteins.

• Project/Area Number: 19K09721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Toin University of Yokohama
• Principal Investigator: Yoshida Kaoru 桐蔭横浜大学, 医用工学部, 教授 (70398973)
• Co-Investigator(Kenkyū-buntansha): 吉田 学 東京大学, 大学院理学系研究科(理学部), 准教授 (60301785)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 精子 / 糖衣 / 精嚢分泌タンパク質 / 卵管 / 受精能獲得 / 精嚢タンパク質 / グリコカリックス / ステロール

Outline of Research at the Start

DEFB126のマウスにおける相同タンパク質はβディフェンシン-22(DEFB22)であり、同様に精子膜表面最外層にグリコカリックスを形成することが示されている。しかしながら、これらグリコカリックスと精嚢分泌タンパク質の相互作用については明らかになっていない。そこで、本研究ではマウスを用い、まず、１）SVS2とDEFB22の相互作用を明らかにする。次
に、２）SVS2およびDEFB22の精子膜からの除去機構をin vivoで検討する。２）で明らかになった機構を手がかりに、３）精子膜ステロールレベル調節について、関わる細胞内外の因子を探索し、同定する。

Outline of Final Research Achievements

Although the efflux of cholesterol from the sperm membrane is triggered during the capacitation, the physiological regulatory mechanism is unknown. We have previously shown that seminal vesicle secretory proteins actively maintain cholesterol levels in the sperm membrane. We hypothesize that this action suppresses ectopic fertilization potential acquisition, but the molecular mechanism is not clear. In this study, mouse utero-tubal junction (UTJ) was cultured for a short time and tissue transparency enabled observation of sperm binding to the oviductal epithelium. In addition, lectin arrays of sperm cell membrane extracts were performed, and it was shown that the sperm cell membrane structure of glycan chains is altered in conjunction with the removal of cholesterol by MbCD and the regulation of the process of fertilization ability acquisition by the presence of sperm seminal vesicle secretory protein SVS2.

Academic Significance and Societal Importance of the Research Achievements

我々を含むほ乳類に共通の体内受精の仕組みを理解することは、挙児を希望するカップルに安全かつ有効な生殖補助医療を提供する基礎となる。特に、本研究のこれまで顧みられることの少なかった精漿成分の体内受精における生理的な役割を明らかにする試みは生殖補助医療への応用も期待できる重要な知見である。

Research Products

• [Journal Article] Identification of an antibacterial polypeptide in mouse seminal vesicle secretions (2021)
  • Author(s): Morohoshi Kazunori、Yamazaki Takeo、Kito Keiji、Sato Ban、Kang Woojin、Hibino Taku、Yoshida Manabu、Yoshida Kaoru、Iwamoto Teruaki、Yamada Mitsutoshi、Miyado Kenji、Kawano Natsuko
  • Journal Title: Journal of Reproductive Immunology Volume: 148 Pages: 103436-103436
  • DOI: 10.1016/j.jri.2021.103436
  • Peer Reviewed / Open Access
• [Journal Article] Human Semenogelin 1 Promotes Sperm Survival in the Mouse Female Reproductive Tract. (2020)
  • Author(s): Sakaguchi D, Miyado K, Iwamoto T, Okada H, Yoshida K, Kang W, Suzuki M, Yoshida M, Kawano N
  • Journal Title: International Journal of Molecular Sciences Volume: 11 Pages: 3961-3961
  • Peer Reviewed / Open Access
• [Journal Article] Deletion of a seminal gene cluster reinforces a crucial role of SVS2 in male fertility. (2019)
  • Author(s): Shindo, M., Inui, M., Kang, W., Tamano, M., Tingwei, C., Takada, S., Hibino, T., Yoshida, M., Yoshida, K., Okada, H., Iwamoto, T., Miyado, K., and Kawano, N.
  • Journal Title: International Journal of Molecular Sciences Volume: 20(18) Pages: 4557-4557
  • Peer Reviewed / Open Access
• [Journal Article] 受精時に見られる精子運動調節 (2019)
  • Author(s): 吉田 薫，吉田 学
  • Journal Title: 細胞 Volume: 51（5） Pages: 253-255