Spink13, an epididymis-specific gene of the Kazal-type serine protease inhibitor (SPINK) family, is essential for the acrosomal integrity and male fertility

J Biol Chem. 2013 Apr 5;288(14):10154-10165. doi: 10.1074/jbc.M112.445866. Epub 2013 Feb 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrosome / metabolism*
  • Amino Acid Sequence
  • Androgens / metabolism
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Epididymis / metabolism*
  • Female
  • Fertility*
  • Fertilization in Vitro
  • Lentivirus / genetics
  • Male
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Proteinase Inhibitory Proteins, Secretory / chemistry
  • Proteinase Inhibitory Proteins, Secretory / physiology*
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Serine Peptidase Inhibitors, Kazal Type
  • Spermatozoa / metabolism
  • Spermatozoa / physiology


  • Androgens
  • Antibodies, Monoclonal
  • Proteinase Inhibitory Proteins, Secretory
  • Serine Peptidase Inhibitors, Kazal Type
  • Spink13 protein, mouse
  • Spink13 protein, rat