New insights into epididymal biology and function

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, 79430, USA.
Human Reproduction Update (Impact Factor: 8.66). 02/2009; 15(2):213-27. DOI: 10.1093/humupd/dmn055
Source: PubMed

ABSTRACT The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions.
A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included.
While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients.
Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

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    • "The male reproductive tract consists of a number of sex accessory organs, including the efferent ducts, epididymis, vas deferens, and seminal vesicle on each side. The efferent ducts, connecting the testis to the epididymis , are formed by mesonephric tubule remodeling, while other structures are mostly derived from the Wolffian duct that degenerates in females (Cornwall, 2009; Hannema and Hughes, 2007; Herpin and Schartl, 2011; Joseph et al., 2009). Testis development is initiated by establishment of a group of specialized epithelial cells during early gonadogenesis, the Sertoli cells, which are derived from the coelomic epithelium at the genital ridge (Brennan and Capel, 2004; Karl and Capel, 1998). "
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited genetic diseases, caused by mutations in PKD1 and/ or PKD2. Infertility and reproductive tract abnormalities in male ADPKD patients are very common and have higher incidence than in the general population. In this work, we reveal novel roles of Pkd2 for male reproductive system development. Disruption of Pkd2 caused dilation of mesonephric tubules/efferent ducts, failure of epididymal coiling, and defective testicular development. Deletion of Pkd2 in the epithelia alone was sufficient to cause reproductive tract defects seen in Pkd2−/− mice, suggesting that epithelial Pkd2 plays a pivotal role for development and maintenance of the male reproductive tract. In the testis, Pkd2 also plays a role in interstitial tissue and testicular cord development. In-depth analysis of epithelial-specific knockout mice revealed that Pkd2 is critical to maintain cellular phenotype and developmental signaling in the male reproductive system. Taken together, our data for the first time reveal novel roles for Pkd2 in male reproductive system development and provide new insights in male reproductive system abnormality and infertility in ADPKD patients.
    Differentiation 03/2014; DOI:10.1016/j.diff.2014.04.001 · 2.84 Impact Factor
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    • "After spermatogenesis in the testis, spermatozoa pass sequentially through the caput and corpus epididymides and are retained in the cauda epididymis where they are stored until ejaculation (Cornwall, 2009). As spermatozoa migrate through the epididymis, they undergo intrinsic biochemical and functional modifications that result in the acquisition of motility and the ability to become capacitated for fertilization (Sullivan et al., 2007). "
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    ABSTRACT: Caput epididymal wild-type spermatozoa and cauda epididymal spermatozoa from mice null for the adenylyl cyclase Adcy10 gene are immotile unless stimulated by a membrane-permeant cyclic AMP analogue. Both types of spermatozoa exhibit flagellar angulation where the head folds back under these conditions. As sperm proteins undergo oxidation of sulfhydryl groups and the flagellum becomes more stable to external forces during epididymal transit, we hypothesized that ADCY10 is involved in a mechanism regulating flagellar stabilization. Although no differences were observed in global sulfhydryl status between caput and cauda epididymal spermatozoa from wild-type or Adcy10-null mice, two-dimensional fluorescence difference gel electrophoresis was performed to identify specific mouse sperm proteins containing sulfhydryl groups that became oxidized during epididymal maturation. A-kinase anchor protein 4, fatty acid-binding protein 9 (FABP9), glutathione S-transferase mu 5 and voltage-dependent anion channel 2 exhibited changes in thiol status between caput and cauda epididymal spermatozoa. The level and thiol status of each of these proteins were quantified in wild-type and Adcy10-null cauda epididymal spermatozoa. No differences in the abundance of any protein were observed; however, FABP9 in Adcy10-null cauda epididymal spermatozoa contained fewer disulfide bonds than wild-type sperm cells. In caput epididymal spermatozoa, FABP9 was detected in the cytoplasmic droplet, principal piece, midpiece, and non-acrosomal area of the head. However, in cauda epididymal spermatozoa, this protein localized to the perforatorium, post-acrosomal region and principal piece. Together, these results suggest that thiol changes during epididymal maturation have a role in the stabilization of the sperm flagellum.
    Andrology 11/2013; 2(1). DOI:10.1111/j.2047-2927.2013.00147.x · 3.37 Impact Factor
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    • "Based on anatomical and functional differences, the epididymis is divided into four segments, the initial segment, caput epididymis, corpus epididymis, and cauda epididymis (Lasserre et al., 2001). Each epididymal segment is confined by connective tissue septa to functionally separate the epididymal regions (Cornwall, 2009). The epithelium of the epididymis is composed of several cell types, including principal, basal, apical, narrow, clear, and halo cells (Arrotéia et al., 2012). "
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    ABSTRACT: Intercellular interactions are important for the proper development and regulation of tissue function. This is especially necessary in the epididymis, a part of male reproductive tract where sperm become mature and acquire their fertilizing capacity. The caput region of the epididymis consists of several types of cells, including principal, basal, and apical cells. Direct intercellular communication is thus required to precisely regulate the functions of the caput epididymis. In this regard, connexin (Cx) is a molecule that forms channels, which allow the direct exchange of small molecules between cells, enabling intercellular communication. In this study, the expression of Cx isoforms in the caput epididymis at different postnatal ages was determined by using quantitative real-time polymerase chain reaction analysis. Nine of 13 Cx isoforms were detected. The transcript levels of Cx30.3, 31, 31.1, 32, and 40 were highest at 45 days of age, while the expression of Cx43 and 45 gradually decreased with age. A substantial fluctuation of Cx26 expression was detected, with significant decreases before and during puberty, followed by a transient increase at adult-hood and rapid decreases at an old age. A significant increase in Cx37 transcript was observed at 25 days of age, followed by gradual decreases at adult and old ages. These results indicate the significant differential expression of various Cx isoforms in the caput epididymis during postnatal development. It further suggests that the functional regulation and developmental maturation of the caput epididymis are highly related to the postnatal age-related differential expression of Cx isoforms.
    08/2013; 55(4). DOI:10.5187/JAST.2013.55.4.249
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