机构：[1]Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital,First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China深圳市第二人民医院深圳医学信息中心[2]Epithelial CellBiology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Educationof China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University ofHong Kong, Hong Kong SAR, China[3]Guangdong and Shenzhen Key Laboratory of MaleReproductive Medicine and Genetics, Institute of Urology, Peking University ShenzhenHospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China[4]ShantouUniversity Medical College, Shantou 515041, China[5]Department of Surgery, Division ofUrology, The Chinese University of Hong Kong, Hong Kong SAR, China[6]SichuanUniversity–The Chinese University of Hong Kong Joint Laboratory for ReproductiveMedicine, Women’s and Children’s Hospital, Sichuan University, Sichuan 610017, China
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.
基金：
National Key Scientific Program of China [2011CB944303, 2013CB967401, 2013CB967403, 2013CB967404]; Research Grants Council of Hong Kong (GRF/UHK) [461213]; National Nature Science Foundation of ChinaNational Natural Science Foundation of China [81070529, 30972992, 81170613, 31100841]; Promotion Program for Shenzhen Key Laboratory [CXB201005250017A]; Shenzhen Projects of Science and Technology [200901015, JC200903180681A]; Biobank of Complex Diseases in Shenzhen [CXC201005260001A]; Focused Investment Scheme of the Chinese University of Hong KongChinese University of Hong Kong; K.S. Lo Foundation
第一作者机构：[1]Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital,First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China[2]Epithelial CellBiology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Educationof China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University ofHong Kong, Hong Kong SAR, China[3]Guangdong and Shenzhen Key Laboratory of MaleReproductive Medicine and Genetics, Institute of Urology, Peking University ShenzhenHospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China
共同第一作者：
通讯作者：
通讯机构：[1]Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital,First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China[2]Epithelial CellBiology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Educationof China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University ofHong Kong, Hong Kong SAR, China[3]Guangdong and Shenzhen Key Laboratory of MaleReproductive Medicine and Genetics, Institute of Urology, Peking University ShenzhenHospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China[6]SichuanUniversity–The Chinese University of Hong Kong Joint Laboratory for ReproductiveMedicine, Women’s and Children’s Hospital, Sichuan University, Sichuan 610017, China
推荐引用方式(GB/T 7714)：
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):doi:10.1126/scitranslmed.3009071.
APA：
Diao, Ruiying,Fok, Kin Lam,Chen, Hao,Yu, Mei Kuen,Duan, Yonggang...&Chan, Hsiao Chang.(2014).Deficient human beta-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection.SCIENCE TRANSLATIONAL MEDICINE,6,(249)
MLA：
Diao, Ruiying,et al."Deficient human beta-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection".SCIENCE TRANSLATIONAL MEDICINE 6..249(2014)
生物