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Andrology Sep 2019The epididymis is the hallmark of all vertebrate species practicing internal fertilization. While the functions of the epididymis are well documented in laboratory... (Review)
Review
BACKGROUND
The epididymis is the hallmark of all vertebrate species practicing internal fertilization. While the functions of the epididymis are well documented in laboratory rodents and some domestic animals, the structure and functions of the epididymis in humans remain poorly documented.
OBJECTIVES
Using human tissues obtained with the collaboration of our local organ transplantation program, the histology, cell types, and three-dimensional organization of the excurrent duct were investigated. Microarrays were performed to determine the gene expression pattern along the human epididymis.
MATERIALS AND METHODS
The histology of longitudinal sections of the proximal epididymis was described, and immunohistochemistry using specific antibodies was used to characterize cell types of the efferent duct and caput epididymis epithelia. The epididymis was divided into eight segments permitting gene profiling by microarray and gene ontology analysis.
RESULTS
The proximal region of the human epididymis is formed exclusively by efferent ducts. These ducts form a complex histological structure particularly at the junction of the efferent ducts and caput epididymis. The efferent ducts exhibit a specific cellular signature when compared with the adjacent epididymis tubule. Efferent duct gene expression is not segmented and is dedicated to cilium differentiation and movement. The gene expression pattern of the caput segment is homogeneous and specialized in defense and immune responses and fertilization.
DISCUSSION
In murine species, the epididymis is segmented into the initial segment, caput, corpus, and cauda regions, whereas in humans, the proximal region is formed by efferent ducts. The caput tubules have their own histological organization with a well-defined gene expression pattern. The distal corpus and cauda epididymis are distinct by a limited number of differentially expressed genes.
CONCLUSIONS
Knowledge of epididymis functions and structure obtained using laboratory species should be extrapolated to humans with caution.
Topics: Cell Differentiation; Epididymis; Epithelial Cells; Epithelium; Humans; Male; Transcriptome
PubMed: 31033221
DOI: 10.1111/andr.12633 -
Asian Journal of Andrology 2016β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant... (Review)
Review
β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility.
Topics: Aging; Animals; Epididymis; Fetus; Gene Expression Regulation; Humans; Male; Spermatozoa; beta-Defensins
PubMed: 26763543
DOI: 10.4103/1008-682X.168791 -
Asian Journal of Andrology 2015The Sixth International Conference on the Epididymis (Epididymis VI: Networks in the Epididymis, Basic and Clinical Research) was held between October 31 and November 3...
The Sixth International Conference on the Epididymis (Epididymis VI: Networks in the Epididymis, Basic and Clinical Research) was held between October 31 and November 3 2014 in Shanghai, China.
Topics: Andrology; Animals; Epididymis; Humans; Male
PubMed: 26208398
DOI: 10.4103/1008-682X.160264 -
International Braz J Urol : Official... 2022
Topics: Epididymis; Humans; Male; Spermatozoa; Vas Deferens
PubMed: 35170898
DOI: 10.1590/S1677-5538.IBJU.2022.9907.1 -
Biology of Reproduction Feb 2011Estrogen's presence in the male reproductive system has been known for over 60 years, but its potential function in the epididymis remains an important area of... (Review)
Review
Estrogen's presence in the male reproductive system has been known for over 60 years, but its potential function in the epididymis remains an important area of investigation. Estrogen is synthesized by germ cells, producing a relatively high concentration in rete testis fluid. There are two estrogen receptors (ESR), the presence of which in the head of the epididymis is well documented and consistent between species; however, in other regions of the epididymis, their expression appears to be isotype, species, and cell specific. ESR1 is expressed constitutively in the epididymis; however, its presence is downregulated by high doses of estrogen, making the design of experiments complicated, as the phenotype of the Cyp19a1(-/-) mouse does not resemble that of the Esr1(-/-) mouse. Ligand-independent and DNA-binding Esr1 mutant models further demonstrate the complexity and importance of both signaling pathways in maintenance of efferent ductules and epididymis. Data now reveal the presence of not only classical nuclear receptors, but also cytoplasmic ESR and rapid responding membrane receptors; however, their importance in the epididymis remains undetermined. ESR1 regulates ion transport and water reabsorption in the efferent ducts and epididymis, and its regulation of other associated genes is continually being uncovered. In the male, some genes, such as Aqp9 and Slc9a3, contain both androgen and estrogen response elements and are dually regulated by these hormones. While estrogen pathways are a necessity for fertility in the male, future studies are needed to understand the interplay between androgens and estrogens in epididymal tissues, particularly in cell types that contain both receptors and their cofactors.
Topics: Animals; Animals, Genetically Modified; Aromatase; Epididymis; Estrogen Antagonists; Estrogen Receptor alpha; Estrogens; Fertility; Genitalia, Male; Humans; Male; Models, Animal; Receptors, Estrogen; Seminiferous Tubules; Signal Transduction
PubMed: 20926801
DOI: 10.1095/biolreprod.110.087353 -
Andrology Sep 2019In most pseudostratified epithelia, basal cells represent a multipotent adult stem cell population. These cells generally remain in a quiescent state, until they are... (Review)
Review
BACKGROUND
In most pseudostratified epithelia, basal cells represent a multipotent adult stem cell population. These cells generally remain in a quiescent state, until they are stimulated to respond to tissue damage by initiating epithelial regeneration. In the epididymis, cell proliferation occurs at a relatively slow rate under normal physiological conditions. Epididymal basal cells have been shown to share common properties with multipotent adult stem cells. The development of organoids from stem cells represents a novel approach for understanding cellular differentiation and characterization of stem cells.
OBJECTIVE
To review the literature on tissue regeneration in the epididymis and demonstrate the presence of an epididymal stem cell population.
METHODS
PubMed database was searched for studies reporting on cell proliferation, regeneration, and stem cells in the epididymis. Three-dimensional cell culture of epididymal cells was used to determine whether these can develop into organoids in a similar fashion to stem cells from other tissues.
RESULTS
The epididymal epithelium can rapidly regenerate following orchidectomy or efferent duct ligation, in order to maintain epithelial integrity. Studies have isolated a highly purified fraction of rat epididymal basal cells and reported that these cells displayed properties similar to those of multipotent adult stem cells. In two-dimensional cell culture conditions, these cells differentiated into cells which expressed connexin 26, a marker of columnar cells, and cytokeratin 8. Furthermore, three-dimensional cell culture of epididymal cells resulted in the formation of organoids, a phenomenon associated with the proliferation and differentiation of stem cells in vitro.
CONCLUSIONS
The rapid proliferation and tissue regeneration of the epididymal epithelium to preserve its integrity following tissue damage as well as the ability of cells to differentiate into organoids in vitro support the notion of a resident progenitor/stem cell population in the adult epididymis.
Topics: Adult Stem Cells; Animals; Cell Proliferation; Connexin 26; Epididymis; Epithelial Cells; Epithelium; Humans; Keratin-8; Male; Rats; Regeneration; Spermatozoa
PubMed: 31033244
DOI: 10.1111/andr.12635 -
Andrology Sep 2019One third of infertility cases in couples worldwide has an exclusive male origin and immune disorders, essentially due to repetitive infections, are emerging an cause of... (Review)
Review
BACKGROUND
One third of infertility cases in couples worldwide has an exclusive male origin and immune disorders, essentially due to repetitive infections, are emerging an cause of male infertility. As the place of sperm maturation, epididymis must be preserved from excessive immune responses that may arise following infections of the male genital tract. At the same time, epididymis must set and maintain a tolerogenic environment in order not to destroy sperm cells that enter the tissue at puberty, long after the immune system has been taught to recognize self pathogens. The immune cells that populate the epididymis have raised growing interest over the last thirty years but they may be not sufficient to understand the immune balance existing in this organ, between immune response to pathogens and tolerance to spermatozoa. Indeed, immune cells are the most motile cells in the organism and need blood and lymphatic vessels to traffic between lymphoid organs and sites of infection to induce efficient responses.
OBJECTIVES
To review the literature on the blood and lymphatic vessels, and on the immune cells present at steady state in the rodent epididymis (rat and mouse).
MATERIALS AND METHODS
PubMed database was searched for studies reporting on the spatial organization of the rodent epididymal vasculature and immune cell types at steady state. This search was combined with recent findings from our team.
RESULTS
At steady state, the rodent epididymis presents with dense blood and lymphatic networks, and a large panel of immune cells distributed across the interstitum and epithelium along the organ.
CONCLUSIONS
The immune system of the rodent epididymis is highly organized. Exploring its functions, especially in an infectious context, is the essential coming step before any transposition to human.
Topics: Animals; Epididymis; Infertility, Male; Lymphatic Vessels; Male; Mice; Rats; Sperm Maturation; Spermatozoa
PubMed: 31106984
DOI: 10.1111/andr.12637 -
Biology of Reproduction May 2011The terms blood-testis barrier (BTB) or blood-epididymis barrier (BEB), are often described as Sertoli cell-Sertoli cell tight junctions (TJs) or TJs between the... (Review)
Review
The terms blood-testis barrier (BTB) or blood-epididymis barrier (BEB), are often described as Sertoli cell-Sertoli cell tight junctions (TJs) or TJs between the epithelial cells in the epididymis, respectively. However, in reality, the BTB and BEB are much more complex than just the TJ. The focus of this minireview is to remind readers that the complete BTB and BEB are comprised of three components: anatomical, physiological, and immunological. The TJs form the anatomical (physical) barrier that restricts passage of molecules and cells from entering or exiting the lumen. The physiological barrier is comprised of transporters that regulate movement of substances in or out of the lumen, thus creating a microenvironment, which is critical for the proper development and maturation of germ cells. The immunological barrier limits access by the immune system and sequesters the majority of the autoantigenic germ cells. Combined with the overall immune-privilege of the testis, this suppresses detrimental immune responses against the autoantigenic germ cells. These three components on their own do not create a complete functional barrier; instead, it is the interaction between all three components that create a barrier of maximal competence.
Topics: Animals; Autoantigens; Blood-Testis Barrier; Epididymis; Humans; Male; Permeability; Spermatogenesis; Spermatozoa; Testis; Tight Junctions
PubMed: 21209417
DOI: 10.1095/biolreprod.110.087452 -
Andrology Sep 2019Our understanding of epididymal physiology and function has been transformed over the three decades in which the International Meeting Series on the Epididymis has been... (Review)
Review
BACKGROUND
Our understanding of epididymal physiology and function has been transformed over the three decades in which the International Meeting Series on the Epididymis has been hosted. This transformation has occurred along many fronts, but among the most significant advances has been the unexpected discovery of the diversity of small non-protein-coding RNAs (sRNAs) expressed in the epididymal epithelium and differentially accumulated in the luminal population of spermatozoa.
OBJECTIVES
Here we survey recent literature pertaining to profiling the sRNA landscape of the mammalian epididymis with the goal of demonstrating the contribution that these key regulatory elements, and their associated pathways, make to epididymal physiology and sperm maturation.
RESULTS AND DISCUSSION
High throughput sequencing strategies have fueled an unprecedented advance in our understanding of RNA biology. In the last decade, such high throughput profiling tools have been increasingly applied to study the mammalian epididymis, presaging the discovery of diverse classes of sRNA expressed along the length of the tract. Among the best studied sRNA classes are the microRNAs (miRNA), a sRNA species shown to act in concert with endocrine signals to fine-tune the segmental patterning of epididymal gene expression. In addition to performing this homeostatic role, epithelial cell-derived sRNAs also selectively accumulate into the epididymosomes and spermatozoa that occupy the duct lumen. This exciting discovery alludes to a novel form of intracellular communication that contributes to the establishment of the sperm epigenome and its modification under conditions of paternal stress.
CONCLUSION
Compelling literature has identified sRNAs as a crucial regulatory tier that allows the epididymis to fulfill its combined roles of sperm transport, maturation, and storage. Continued research in this emerging field will contribute to our growing understanding of the etiology of male factor infertility and potentially allow for the future design of rational therapeutic options for these individuals.
Topics: Animals; Cellular Microenvironment; Epididymis; Epithelium; Humans; Male; MicroRNAs; RNA, Small Interfering; Sperm Maturation; Spermatozoa
PubMed: 31020794
DOI: 10.1111/andr.12640 -
Biology of Reproduction Jul 2016The mammalian epididymis is more than a highly convoluted tube divided into four regions: initial segment, caput, corpus and cauda. It is a highly segmented structure... (Review)
Review
The mammalian epididymis is more than a highly convoluted tube divided into four regions: initial segment, caput, corpus and cauda. It is a highly segmented structure with each segment expressing its own and overlapping genes, proteins, and signal transduction pathways. Therefore, the epididymis may be viewed as a series of organs placed side by side. In this review we discuss the contributions of septa that divide the epididymis into segments and present hypotheses as to the mechanism by which septa form. The mechanisms of Wolffian duct segmentation are likened to the mechanisms of segmentation of the renal nephron and somites. The renal nephron may provide valuable clues as to how the Wolffian duct is patterned during development, whereas somitogenesis may provide clues as to the timing of the development of each segment. Emphasis is also placed upon how segments are differentially regulated, in support of the idea that the epididymis can be considered a series of multiple organs placed side by side. One region in particular, the initial segment, which consists of 2 or 4 segments in mice and rats, respectively, is unique with respect to its regulation and vascularity compared to other segments; loss of development of these segments leads to male infertility. Different ways of thinking about how the epididymis functions may provide new directions and ideas as to how sperm maturation takes place.
Topics: Animals; Epididymis; Fertility; Humans; Male; Sperm Maturation; Spermatogenesis
PubMed: 27122633
DOI: 10.1095/biolreprod.116.138768