Male Reproductive Tract

Gene and Protein Expression in the Epididymis of Infertile c-ros Receptor Tyrosine Kinase-Deficient Mice

Abstract
Transgenic male mice bearing inactive mutations of the receptor tyrosine kinase c-ros lack the initial segment of the epididymis and are infertile. Several techniques were applied to determine differences in gene expression in the epididymal caput of heterozygous fertile (HET) and infertile homozygous knockout (KO) males that may explain the infertility. Complementary DNA arrays, gene chips, Northern and Western blots and immunohistochemistry indicated that some proteins were down-regulated, including the initial segment/proximal caput-specific genes c-ros, cystatin-related epididymal-spermatogenic (CRES) and lipocalin mouse epididymal protein 17 (MEP17), whereas other caput-enriched genes (glutathione peroxidase 5, a disintegrin and metalloproteinase (ADAM7), bone morphogenetic proteins 7 and 8a, A-raf, CCAAT/enhancer binding protein , PEA3) were unchanged. Genes normally absent from the initial segment (-glutamyltranspeptidase, prostaglandin D₂ synthetase, alkaline phosphatase) were expressed in the undifferentiated proximal caput of the knockout. More distally lipocalin 2 (24p3), CRISP1 (formerly MEP7), PEBP (MEP9) and mE-RABP (MEP10) were unchanged in expression. Immunohistochemistry and Western blots confirmed the absence of CRES in epididymal tissue and fluid and the continued presence of CRES in spermatozoa of the knockout mouse. The glutamate transporters EAAC1 (EAAT3) and EAAT5 were down- and up-regulated, respectively. The genes of over 70 transporters, channels and pores were detected in the caput epididymidis but in the knockout only 3 were down-regulated and 6 upregulated. The changes in these genes could affect sperm function by modifying the composition of epididymal fluid and explain the infertility of the KO males. These genes may be targets for a post-testicular contraceptives.

Key words: Gamete Biology • Male Reproductive Tract • Epididymis • Gene regulation • Sperm maturation

This article has been cited by other articles:

				L. Hermo, N. Korah, M. Gregory, L. Y. Liu, D. G. Cyr, A. D'Azzo, and C. E. Smith Structural Alterations of Epididymal Epithelial Cells in Cathepsin A Deficient Mice Affect the Blood-Epididymal Barrier and Lead to Altered Sperm Motility J Androl, September 1, 2007; 28(5): 784 - 797. [Abstract] [Full Text] [PDF]

				D. S. Johnston, S. A. Jelinsky, H. J. Bang, P. DiCandeloro, E. Wilson, G. S. Kopf, and T. T. Turner The Mouse Epididymal Transcriptome: Transcriptional Profiling of Segmental Gene Expression in the Epididymis Biol Reprod, September 1, 2005; 73(3): 404 - 413. [Abstract] [Full Text] [PDF]

				T. R. Chauvin and M. D. Griswold Androgen-Regulated Genes in the Murine Epididymis Biol Reprod, August 1, 2004; 71(2): 560 - 569. [Abstract] [Full Text] [PDF]

				C.-H. Yeung, M. Anapolski, I. Setiawan, F. Lang, and T. G. Cooper Effects of Putative Epididymal Osmolytes on Sperm Volume Regulation of Fertile and Infertile c-ros Transgenic Mice J Androl, March 1, 2004; 25(2): 216 - 223. [Abstract] [Full Text] [PDF]