Journal of Andrology
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Published-Ahead-of-Print June 6, 2007, DOI:10.2164/jandrol.107.002964

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Kim Boekelheide
John M Sedivy
Jan Klysik
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Mice lacking Raf Kinase Inhibitor Protein-1 (RKIP-1) have altered sperm capacitation and reduced reproduction rates with a normal response to testicular injury

Jeffrey S Moffit , Kim Boekelheide , John M Sedivy , and Jan Klysik *

* To whom correspondence should be addressed. E-mail: jan_klysik{at}brown.edu.

Raf Kinase Inhibitor Protein (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 ERK, NF-{kappa}B, and 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 TUNEL positivity 9h 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 to their wild type counterparts. Data from mating experiments indicate decreased reproduction rates between crosses of RKIP-1-/- 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 • RKIP • capacitation • sperm • testis







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