title: Deficient human β-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection.
abstract: 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 β-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 Ca(2+) 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.
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors.forename: Ruiying
authors.initials: R
authors.lastname: Diao
authors.affiliation: Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kin Lam
authors.initials: KL
authors.lastname: Fok
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Mei Kuen
authors.initials: MK
authors.lastname: Yu
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chin Man
authors.initials: CM
authors.lastname: Chung
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China. Shantou University Medical College, Shantou 515041, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Hanwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Zesong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China. Shantou University Medical College, Shantou 515041, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China. Shantou University Medical College, Shantou 515041, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Zhen
authors.affiliation: Department of Surgery, Division of Urology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chi Fai
authors.initials: CF
authors.lastname: Ng
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China. hsiaocchan@cuhk.edu.hk caizhiming2000@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, Women's and Children's Hospital, Sichuan University, Sichuan 610017, China. hsiaocchan@cuhk.edu.hk caizhiming2000@163.com.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D020013:Calcium Signaling; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008954:Models, Biological; D011485:Protein Binding; D054399:Receptors, CCR6 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D060737:Reproductive Tract Infections / Q000378:metabolism* / Q000473:pathology*; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism; D023083:beta-Defensins / Q000172:deficiency* / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; C406407:DEFB1 protein, human; D054399:Receptors, CCR6; D011994:Recombinant Proteins; D023083:beta-Defensins