title: Spink13, an epididymis-specific gene of the Kazal-type serine protease inhibitor (SPINK) family, is essential for the acrosomal integrity and male fertility.
abstract: Sperm maturation involves numerous surface modifications by a variety of secreted proteins from epididymal epithelia. The sperm surface architecture depends on correct localization of its components and highlights the importance of the sequence of the proteolytic processing of the sperm surface in the epididymal duct. The presence of several protease inhibitors from different families is consistent with the hypothesis that correctly timed epididymal protein processing is essential for proper sperm maturation. Here we show that the rat (Rattus norvegicus) epididymis-specific gene Spink13, an androgen-responsive serine protease inhibitor, could bind to the sperm acrosome region. Furthermore, knockdown of Spink13 in vivo dramatically enhanced the acrosomal exocytosis during the process of capacitation and thus led to a significant reduction in male fertility, indicating that Spink13 was essential for sperm maturation. We conclude that blockade of SPINK13 may provide a new putative target for post-testicular male contraceptives.
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China; Graduate University of the Chinese Academy of Sciences, 200031 Shanghai, China.
authors: Li
authors: L
authors: Ma
authors: National Population and Family Planning Commission Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 200032 Shanghai, China.
authors: Heguo
authors: H
authors: Yu
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China.
authors: Zimei
authors: Z
authors: Ni
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China; Graduate University of the Chinese Academy of Sciences, 200031 Shanghai, China.
authors: Shuanggang
authors: S
authors: Hu
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China; Graduate University of the Chinese Academy of Sciences, 200031 Shanghai, China.
authors: Wubin
authors: W
authors: Ma
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China; Graduate University of the Chinese Academy of Sciences, 200031 Shanghai, China.
authors: Chen
authors: C
authors: Chu
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China. Electronic address: qliu@sibcb.ac.cn.
authors: Qiang
authors: Q
authors: Liu
authors: Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China; National Population and Family Planning Commission Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 200032 Shanghai, China. Electronic address: ylzhang@sibcb.ac.cn.
authors: Yonglian
authors: Y
authors: Zhang
mesh_terms: D000177:Acrosome / Q000378:metabolism*; D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D004822:Epididymis / Q000378:metabolism*; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D000074162:Serine Peptidase Inhibitors, Kazal Type; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology
chemical_list: D000728:Androgens; D000911:Antibodies, Monoclonal; D053491:Proteinase Inhibitory Proteins, Secretory; D000074162:Serine Peptidase Inhibitors, Kazal Type; C581324:Spink13 protein, mouse; C581323:Spink13 protein, rat