This Article Full Text Full Text (PDF) All Versions of this Article: 28/6/883    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moffit, J. S. Articles by Klysik, J. Search for Related Content PubMed PubMed Citation Articles by Moffit, J. S. Articles by Klysik, J.

Mice Lacking Raf Kinase Inhibitor Protein-1 (RKIP-1) Have Altered Sperm Capacitation and Reduced Reproduction Rates With a Normal Response to Testicular Injury

JOHN M. SEDIVY

JAN KLYSIK

From the ^* Department of Pathology and Laboratory Medicine and Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI

Correspondence to: Jan Klysik, Brown University, Department of Molecular Biology Cell Biology and Biochemistry, Division of Biology and Medicine, 70 Ship St, Providence, RI 02912 (e-mail: Jan_Klysik{at}Brown.edu).

Raf kinase inhibitor protein-1 (RKIP-1) belongs to the phosphatidyl ethanolamine–binding family of proteins (PEBP), which are highly conserved throughout evolution and widely expressed in tissues of mammalian organisms. RKIP-1 is a modulator of extracellular signal-regulated kinase (ERK), nuclear factor-kappa B (NF-B), and G protein coupled receptor (GPCR) signaling cascades and is implicated as a factor in numerous physiological processes and disease states including metastasis. Testicular germ cells also express high levels of RKIP mRNA during spermatogenesis, particularly from late pachytene spermatocytes through step 15 elongate spermatids. Therefore, the sensitivity of spermatogenesis to injury was compared in wild-type and RKIP-1^-/- mice. Unlike what has been described with tumor suppressors such as p53, RKIP-1^-/- and wild-type mice were equally sensitive to germ cell toxicity by x-irradiation as assessed by terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) positivity 9 hours after a 5 Gy exposure and testicular spermatid head counts 15.5 days after 0.5 Gy exposure. Recent findings also indicate that RKIP is a decapacitation factor receptor on sperm. The present study demonstrates that sperm from RKIP-deficient mice are precociously capacitated compared with their wild-type counterparts. Data from mating experiments indicate decreased reproduction rates between crosses of RKIP-1^-/- male mice and either heterozygous or RKIP-1^-/- females. Furthermore, RKIP immunolocalization of epididymal sperm supports transfer of the protein from germ cell cytoplasm to the sperm via the cytoplasmic droplet during epididymal transport. Overall, these studies indicate an important role for RKIP in reproduction as a modulator of capacitation but not in the regulation of testicular injury.

     Key words: PEBP, testis

This article has been cited by other articles:

				C. L. Borg, K. M. Wolski, G. M. Gibbs, and M. K. O'Bryan Phenotyping male infertility in the mouse: how to get the most out of a 'non-performer' Hum. Reprod. Update, March 1, 2010; 16(2): 205 - 224. [Abstract] [Full Text] [PDF]

				O. D'Amours, G. Frenette, M. Fortier, P. Leclerc, and R. Sullivan Proteomic comparison of detergent-extracted sperm proteins from bulls with different fertility indexes Reproduction, March 1, 2010; 139(3): 545 - 556. [Abstract] [Full Text] [PDF]

				A. Menoret, J. P. McAleer, S.-M. Ngoi, S. Ray, N. A. Eddy, G. Fenteany, S.-J. Lee, R. J. Rossi, B. Mukherji, D. L. Allen, et al. The Oxazolidinone Derivative Locostatin Induces Cytokine Appeasement J. Immunol., December 1, 2009; 183(11): 7489 - 7496. [Abstract] [Full Text] [PDF]

				G. M. Gibbs, K. Roelants, and M. K. O'Bryan The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins--Roles in Reproduction, Cancer, and Immune Defense Endocr. Rev., December 1, 2008; 29(7): 865 - 897. [Abstract] [Full Text] [PDF]

				A. I Yudin, T. L Tollner, C. A Treece, R. Kays, G. N Cherr, J. W Overstreet, and C. L Bevins {beta}-Defensin 22 is a major component of the mouse sperm glycocalyx Reproduction, December 1, 2008; 136(6): 753 - 765. [Abstract] [Full Text] [PDF]