Gene Expression and Epididymal Function

Cornwall, Gail A.; Lareyre, Jean‐Jacques; Matusik, Robert J.; Hinton, Barry T.; Orgebin‐Crist, Marie‐Claire

doi:10.1007/978-1-4615-0679-9_10

Cited by 58 publications

(68 citation statements)

References 188 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, several epididymal proteins have been shown to be involved in epididymal sperm maturation, and several proteins and protein families expected to be important in regulating the sperm maturation process have been identified, though not fully characterized. Many of these proteins have been described previously in several review articles (Kirchhoff 1999, Cornwall et al 2002. The advanced high-throughput methods such as expression profiling and in silico analyses together with targeted mutagenesis in mice are expected to speed up the identification and functional validation of the key players in the sperm maturation process.…”

Section: Discussionmentioning

confidence: 99%

Novel epididymal proteins as targets for the development of post-testicular male contraception

Sipilä

Jalkanen²,

Huhtaniemi³

et al. 2009

Reproduction

View full text Add to dashboard Cite

Apart from condoms and vasectomy, modern contraceptive methods for men are still not available. Besides hormonal approaches to stop testicular sperm production, the post-meiotic blockage of epididymal sperm maturation carries lots of promise. Microarray and proteomics techniques and libraries of expressed sequence tags, in combination with digital differential display tools and publicly available gene expression databases, are being currently used to identify and characterize novel epididymal proteins as putative targets for male contraception. The data reported indicate that these technologies provide complementary information for the identification of novel highly expressed genes in the epididymis. Deleting the gene of interest by targeted ablation technology in mice or using immunization against the cognate protein are the two preferred methods to functionally validate the function of novel genes in vivo. In this review, we summarize the current knowledge of several epididymal proteins shown either in vivo or in vitro to be involved in the epididymal sperm maturation. These proteins include CRISP1, SPAG11e, DEFB126, carbonyl reductase P34H, CD52, and GPR64. In addition, we introduce novel proteinases and protease inhibitor gene families with potentially important roles in regulating the sperm maturation process. Furthermore, potential contraceptive strategies as well as delivery methods will be discussed. Despite the progress made in recent years, further studies are needed to reveal further details in the epididymal sperm maturation process and the factors involved, in order to facilitate the development of new epididymal contraceptives.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel epididymal proteins as targets for the development of post-testicular male contraception

Sipilä

Jalkanen²,

Huhtaniemi³

et al. 2009

Reproduction

View full text Add to dashboard Cite

show abstract

“…sperm maturation) requires the successive exposure of spermatozoa to the particular luminal environment created by different epididymal regions (Orgebin-Crist 1967, Robaire & Hinton 2002. The functional segmentation of the epididymis is reflected at the molecular level by complex region-specific gene expression profiles (Jervis & Robaire 2001, Cornwall et al 2002. The unique patterns of gene expression along the duct contribute to the evolving repertoire of components that make up the highly specialized luminal fluid.…”

Section: Introductionmentioning

confidence: 99%

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

Henderson¹,

Cooke²,

Robaire³

2006

Journal of Endocrinology

View full text Add to dashboard Cite

Dihydrotestosterone (DHT) is the primary androgen acting in the epididymis, the site of sperm maturation. Previously, we showed that the treatment of male rats with PNU157706, an inhibitor that acts on both isoforms of 5a-reductase to prevent DHT formation, has effects on the expression of genes implicated in processes that create the optimal luminal microenvironment required for sperm maturation, and on sperm maturation itself. However, signaling pathways involved in regulating or mediating DHT actions in the epididymis remain largely unknown. The goals of this study were to determine the expression profiles of potential signaling systems in the epididymis and assess their DHTdependence using two different dual 5a-reductase inhibitors. Rats were untreated or gavaged with vehicle, 10 mg/kg per day PNU157706 or 32 mg/kg per day FK143 for 28 days and epididymal gene expression was analyzed. Gene array analysis revealed analogous effects of FK143 on overall epididymal gene expression when compared with previous PNU157706 studies. Quantitative RT-PCR analysis of the expression of the 5a-reductase isozymes, androgen receptor, and members of the IGF, FGF, TGF, and VEGF families revealed novel region-specific expression profiles in the epididymis that were differentially affected by 5a-reductase inhibition; the two inhibitors had parallel effects. Specifically, in proximal regions, 5a-reductase 1, androgen receptor, and TGF-b1 expression increased after treatment, while in distal regions expression of IGF-I, IGFBP-5, IGFBP-6, and FGF-10 decreased. These results provide insight into epididymal signaling mechanisms and indicate potential candidates acting either upstream or downstream of DHT to regulate and/or mediate its actions in the epididymis.

show abstract

“…The expression patterns of several epididymis-specific and/or epididymis-relevant genes have been analyzed along the epididymis (for review see Cornwall et al 2002); however, understanding the structure and function of this complex tissue requires more than analyzing the properties of isolated genes. The biological function of sperm maturation arises from the interactions of many components.…”

Section: Introductionmentioning

confidence: 99%

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis

Henderson¹,

Cooke²,

Robaire³

2004

Journal of Endocrinology

View full text Add to dashboard Cite

The epididymis is the site of sperm maturation and storage. 5 -Reductases (types 1 and 2) are key enzymes in this tissue because they convert testosterone to dihydrotestosterone (DHT), the main androgen regulating epididymal functions. Examining the consequences of inhibiting DHT formation is likely to provide important information regarding the regulation of epididymal functions, yet few inhibitor studies have focused on this tissue. To understand better DHT-mediated regulation of epididymal gene expression, we employed a dual 5 -reductase inhibitor and cDNA microarrays to examine the effects of 5 -reductase inhibition on gene expression in the initial segment, caput, corpus, and cauda epididymidis. Inhibition of epididymal 5 -reductase activity by PNU157706 was confirmed by in vitro enzyme assays. Rats were treated with 0, 0·1, 1·0 or 10 mg/kg per day PNU157706 for 28 days. The weights of DHT-dependent tissues, including the epididymis, were decreased following treatment. The effect of treatment on gene expression was dose-dependent and highly segment-specific. The initial segment responded uniquely in that a similar number of genes increased and decreased in expression compared with the other segments where the majority of affected genes decreased in expression. Some of the more dramatically affected genes were involved in signal transduction as well as fatty acid and lipid metabolism, regulation of ion and fluid transport, luminal acidification, oxidative defense and protein processing and degradation. These are essential processes contributing to the formation of an optimal luminal microenvironment required for proper sperm maturation. These results provide a novel insight into the DHT-dependent mechanisms that control epididymal functions.

show abstract

Gene Expression and Epididymal Function

Cited by 58 publications

References 188 publications

Novel epididymal proteins as targets for the development of post-testicular male contraception

Novel epididymal proteins as targets for the development of post-testicular male contraception

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

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis

Contact Info

Product

Resources

About