The Mouse Epididymal Transcriptome: Transcriptional Profiling of Segmental Gene Expression in the Epididymis1

Abstract

Maturation of spermatozoa, including the acquisition of motility and the ability to undergo capacitation, occurs during transit through the dynamic environment of the epididymis. The microenvironments created along the length of the epididymal tubule are essential to the molecular modifications of spermatozoa that result in fertile gametes. The secretory and resorptive processes of the epithelial cells that line this tubule generate these microenvironments. In the current study, 10 morphologically distinct segments of the mouse epididymis were identified by microdissection. We hypothesized that the changing environments of the epididymal lumen are established by differential gene expression among these segments. RNA isolated from each of the 10 segments was analyzed by microarray analysis. More than 17,000 genes are expressed in the mouse epididymis, compared with about 12,000 genes identified from whole epididymal samples. Screening a panel of normal mouse tissues identified both epididymal-selective and epididymal-specific transcripts. In addition, this study identified 2168 genes that are up-regulated or down-regulated by greater than 4-fold between at least two different segments. The expression patterns of these genes identify distinct patterns of segmental regulation. Using principal component analysis, we determined that the 10 segments form 6 different transcriptional units. These analyses elucidate the changes in gene expression along the length of the epididymis for 17,000 expressed transcripts and provide a powerful resource for the research community in future studies of the biological factors that mediate epididymal sperm maturation.

Segment- And Cell-Specific Expression of Dtype Cyclins in the Postnatal Mouse Epididymis

“…Our data indicate that these proteins are expressed in a spatiotemporally exclusive pattern that is nearly parallel to that reported for the corresponding mRNAs using a large-scale expression profiling method and deposited at http://mrg.gs.washington.edu/cgibin (Johnston et al, 2005). …”

“…Recent studies have identified dynamic gene expression patterns along the mouse, rat and human epididymal segments and many genes including cell cycle regulators show segment specific expression pattern (Dube et al, 2007;Jelinsky et al, 2007;Johnston et al, 2005;Turner et al, 2007a). However, it is unknown if similar expression patterns occur in parallel in the corresponding proteins encoded by these genes in various segments.…”

Why are epididymal tumours so rare?

“…16 Dysfunction of RB1 is associated with many human cancers. 17 Rb1 RNA is expressed in the mouse, 18 rat 19 and human epididymis. 20 The expression of the tumour suppressor genes Pten and Rb1 counter-balances the activity of pro-proliferative signal proteins in the proximal epididymis of mice.…”

“…The expression of K-Ras, B-Raf and Myc, expressed in the adult human epididymis, 20 enhances the basal expression of the transcription factor Nrf2 (nuclear factor E2-related factor 2), which controls intracellular levels of ROS through an inducible antioxidant programme. 47 Nfe2l2 (Nrf2) mRNA is highly expressed throughout the rat 19 and mouse epididymis 18 and also found in that of man. 20 Adult Nrf2 2/2 male mice suffer reduced antioxidants and raised lipid peroxidation in the epididymis, accompanied by reduced epididymal sperm motility.…”

Vezatin, a ubiquitous protein of adherens cell–cell junctions, is exclusively expressed in germ cells in mouse testis

“…Once the spermatozoon is released to the lumen, it travels through rete testis and epididymis. There, it is confronted to a complex and specific microenvironment, which varies along the epididymis (Johnston et al 2005, Sullivan et al 2005. This complex fluid interacts with the sperm surface and induces its acquisition of motility and fertilizing abilities (Orgebin-Crist 1967, Zhou et al 2004.…”