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学科主题: 临床医学
题名:
Deficient human beta-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection
作者: Diao, Ruiying1,2,3; Fok, Kin Lam2; Chen, Hao1,2,3; Yu, Mei Kuen2; Duan, Yonggang1,3; Chung, Chin Man2; Li, Zhao3,4; Wu, Hanwei1; Li, Zesong1; Zhang, Hu3,4; Ji, Ziliang3,4; Zhen, Wanhua1; Ng, Chi Fai5; Gui, Yaoting3; Cai, Zhiming1,3; Chan, Hsiao Chang2,6
刊名: SCIENCE TRANSLATIONAL MEDICINE
发表日期: 2014-08-13
DOI: 10.1126/scitranslmed.3009071
卷: 6, 期:249
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]: Cell Biology ; Research & Experimental Medicine
关键词[WOS]: MALE REPRODUCTIVE-TRACT ; ANTIMICROBIAL ACTIVITY ; INJECTION ICSI ; MALE-FERTILITY ; HOST-DEFENSE ; SEMEN ; EPIDIDYMIS ; PROTEINS ; MICE ; LEUKOCYTOSPERMIA
英文摘要:

Genital tract infection and reduced sperm motility are considered two pivotal etiological factors for male infertility associated with leukocytospermia and asthenozoospermia, respectively. We demonstrate that the amount of human beta-defensin 1 (DEFB1) in sperm from infertile men exhibiting either leukocytospermia or asthenozoospermia, both of which are associated with reduced motility and reduced bactericidal activity in sperm, is much lower compared to that in normal fertile sperm. Interference with DEFB1 function also decreases both motility and bactericidal activity in normal sperm, whereas treatment with recombinant DEFB1 markedly restores DEFB1 expression, bactericidal activity, sperm quality, and egg-penetrating ability in sperm from both asthenozoospermia and leukocytospermia patients. DEFB1 interacts with chemokine receptor type 6 (CCR6) in sperm and triggers Ca2+ mobilization, which is important for sperm motility. Interference with CCR6 function also reduces motility and bactericidal activity of normal sperm. The present finding explains a common defect in male infertility associated with both asthenozoospermia and leukocytospermia, indicating a dual role of DEFB1 in defending male fertility. These results also suggest that the expression of DEFB1 and CCR6 may have diagnostic potential and that treatment of defective sperm with recombinant DEFB1 protein may be a feasible therapeutic approach for male infertility associated with poor sperm motility and genital tract infection.

语种: 英语
所属项目编号: 2011CB944303 ; 2013CB967401 ; 2013CB967403 ; 2013CB967404 ; 461213 ; 81070529 ; 30972992 ; 81170613 ; 31100841 ; CXB201005250017A ; 200901015 ; JC200903180681A ; CXC201005260001A
项目资助者: National Key Scientific Program of China ; Research Grants Council of Hong Kong (GRF/UHK) ; National Nature Science Foundation of China ; Promotion Program for Shenzhen Key Laboratory ; Shenzhen Projects of Science and Technology ; Biobank of Complex Diseases in Shenzhen ; Focused Investment Scheme of the Chinese University of Hong Kong ; K.S. Lo Foundation
WOS记录号: WOS:000340938300003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64826
Appears in Collections:北京大学深圳医院_期刊论文

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作者单位: 1.Shantou Univ, Coll Med, Shantou 515041, Peoples R China
2.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen Key Lab Genitourinary Tumor, Shenzhen 518035, Peoples R China
3.Chinese Univ Hong Kong, Fac Med, Epithelial Cell Biol Res Ctr, Sch Biomed Sci,Key Lab Regenerat Med,Minist Educ, Hong Kong, Hong Kong, Peoples R China
4.Peking Univ, Shenzhen Hosp, Shenzhen PKU HKUST Med Ctr, Inst Urol,Guangdong & Shenzhen Key Lab Male Repor, Shenzhen 518036, Peoples R China
5.Chinese Univ Hong Kong, Dept Surg, Div Urol, Hong Kong, Hong Kong, Peoples R China
6.Sichuan Univ, Chinese Univ Hong Kong, Womens & Childrens Hosp, Joint Lab Reprod Med, Chengdu 610017, Sichuan, Peoples R China

Recommended Citation:
Diao, Ruiying,Fok, Kin Lam,Chen, Hao,et al. Deficient human beta-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection[J]. SCIENCE TRANSLATIONAL MEDICINE,2014,6(249).
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