Gene Expression Is Differentially Regulated in the Epididymis after Orchidectomy

Abstract

The epididymis is the site for the transport, maturation, and storage of spermatozoa. Regulation of epididymal structure and function is highly dependent on the ipsilateral testis. At the molecular level, however, few studies have been undertaken to determine which genes are expressed in the epididymis under testicular regulation. The goal of this study was to identify genes for which expression is regulated after orchidectomy, both throughout the epididymis and in a segment-specific manner. Microarrays spotted with 474 rat cDNAs were used to examine gene expression changes over the first 7 d post orchidectomy in the initial segment, caput, corpus, and cauda epididymidis of the adult Brown Norway rat. Using k-means cluster analysis, we show that four patterns of gene expression are activated in each epididymal segment over the first week following orchidectomy. Transient up-regulation of gene expression in the epididymis after orchidectomy is described for the first time. Potential androgen-repressed genes, including Gpx-1, show increased expression in the epididymis after orchidectomy. Several glutathione-S-transferases and calcium-binding proteins decline throughout the epididymis after orchidectomy, indicating that these may be novel androgen-regulated epididymal genes. Other genes coding for metabolism-associated proteins, transporters, and alpha-1 acid glycoprotein show segment-specific regulation in the epididymis after orchidectomy. Finally, we describe the expression of the previously uncharacterized heat shock proteins, and apoptosis-associated genes in the epididymis after orchidectomy. Thus, gene expression in the epididymis is differentially affected over time after orchidectomy. These results provide novel insight into androgen-dependent and segment-specific epididymal function.

Identification, characterization, and evolution of a primate β-defensin gene cluster

“…33 The expression of defensins was not affected by castration in the corpus region, while caudal expression of defensins DEFB118-DEFB123 was not maintained at normal levels by exogenous testosterone, suggesting the requirement for additional testis factors as suggested previously. 25 Principal cells are particularly sensitive to circulating androgens and the androgen regulation of beta defensins may be cell and tissue specific.…”

Androgens and the male reproductive tract: an overview of classical roles and current perspectives

“…In fact, the control of gene transcription by androgens varies along the epididymis and is differentially affected with progression of surgical castration (65). Microarray analysis of 474 genes was used to evaluate gene expression changes over the first seven days postsurgical castration in the initial segment, caput, corpus, and cauda epididymis from adult rats.…”

“…Microarray analysis of 474 genes was used to evaluate gene expression changes over the first seven days postsurgical castration in the initial segment, caput, corpus, and cauda epididymis from adult rats. Several genes encoding proteins involved in cell viability and metabolism, as well as sperm maturation, were shown to be androgen-regulated (65). Microarray analysis of 31,000 genes indicated that, of the 1,059 genes that were affected by surgical castration after seven days, DHT treatment for seven consecutive days was capable of restoring over 75% of the gene levels toward the control, indicating that testosterone and DHT may differentially regulate the relative levels of such gene transcripts along rat epididymis (58).…”

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

“…Importantly, distinctive region-specific epididymal gene expression changes also occur during aging and in response to other experimental manipulations, such as orchidectomy, caloric restriction, and vitamin E treatments (Jervis & Robaire 2002, Ezer & Robaire 2003. These responses clearly demonstrate the differential regulation of this tissue, however, surprisingly, little is known about how this regulation is achieved.…”