Alterations in the Human Blood-Epididymis Barrier in Obstructive Azoospermia and the Development of Novel Epididymal Cell Lines from Infertile Men1

Dubé, Évemie; Hermo, Louis; Chan, Peter; Cyr, Daniel G.

doi:10.1095/biolreprod.110.084459

Cited by 26 publications

(11 citation statements)

References 52 publications

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“…AR , androgen receptor; ER ‐α, estrogen receptor‐alpha; ER ‐β, estrogen receptor‐beta; FHCE , fertile human caput epididymal cell line; IHCE , infertile human caput epididymal cell line; RAR ‐β, retinoid acid receptor beta; TR ‐β, thyroid hormone receptor‐beta. This illustration summarizes the findings reported in Dubé et al (2010 a , b ).…”

Section: Dcxr and Disease – The Multifunctional Nature Of Dcxrsupporting

confidence: 63%

“…Consequently, altered expression of genes coding for cell junctional proteins in the principal cells of the epididymis will affect epididymal sperm maturation and hence the sperm's ability to fertilize. To identify alterations in the expression of cell‐adhesion molecules associated with human infertility, Dubé et al (2010 a , b ) established several immortalized caput epididymal cell lines from either a fertile patient (FHCE, fertile human caput epididymal cell line) or an infertile patient with obstructive azoospermia (IHCE, infertile human caput epididymal cell line).…”

Section: Dcxr and Disease – The Multifunctional Nature Of Dcxrmentioning

confidence: 99%

“…In one of the ‘infertile’ cell lines, clone IHCE1, several epididymal markers including DCXR were absent at the mRNA level, as well as differentiation markers (Dubé et al , 2010 b ). Although both cell lines (FHCE and IHCE) expressed the epithelial marker cytokeratin, the flattened cell shape of IHCE1 indicated their de‐differentiated state, characteristic of cells undergoing an EMT.…”

Section: Dcxr and Disease – The Multifunctional Nature Of Dcxrmentioning

confidence: 99%

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Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

Ebert¹,

Kisiela²,

Maser³

2014

Biological Reviews

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Dicarbonyl/L-xylulose reductase (DCXR; SDR20C1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily catalyzes the reduction of α-dicarbonyl compounds and monosaccharides. Its role in the metabolism of L-xylulose has been known since 1970, when essential pentosuria was found to be associated with DCXR deficiency. Despite its early discovery, our knowledge about the role of human DCXR in normal physiology and pathophysiology is still incomplete. Sporadic studies have demonstrated aberrant expression in several cancers, but their physiological significance is unknown. In reproductive medicine, where DCXR is commonly referred to as 'sperm surface protein P34H', it serves as marker for epididymal sperm maturation and is essential for gamete interaction and successful fertilization. DCXR exhibits a multifunctional nature, both acting as a carbonyl reductase and also performing non-catalytic functions, possibly resulting from interactions with other proteins. Recent observations associate DCXR with a role in cell adhesion, pointing to a novel function involving tumour progression and possibly metastasis. This review summarizes the current knowledge about human DCXR and its orthologs from mouse and Caenorhabditis elegans (DHS-21) with an emphasis on its multifunctional characteristics. Due to its close structural relationship with DCXR, carbonyl reductase 2 (Cbr2), a tetrameric enzyme found in several non-primate species is also discussed. Similar to human DCXR, Cbr2 from golden hamster (P26h) and cow (P25b) is essential for sperm-zona pellucida interaction and fertilization. Because of the apparent similarity of these two proteins and the inconsistent use of alternative names previously, we provide an overview of the systematic classification of DCXR and Cbr2 and a phylogenetic analysis to illustrate their ancestry.

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Section: Dcxr and Disease – The Multifunctional Nature Of Dcxrsupporting

confidence: 63%

Section: Dcxr and Disease – The Multifunctional Nature Of Dcxrmentioning

confidence: 99%

Section: Dcxr and Disease – The Multifunctional Nature Of Dcxrmentioning

confidence: 99%

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Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

Ebert¹,

Kisiela²,

Maser³

2014

Biological Reviews

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“…This barrier controls the composition of the epididymal fluid and provides protection to auto-antigenic spermatozoa in an immuno-privileged environment. Interestingly, Cldn10 mRNA expression is altered in patients with obstructive azoospermia [64] and the localization of Cldn10 in the epididymal epithelium is modified in infertile patients with non-obstructive azoospermia [65]. Our observation regarding the regulation of Cldn10 by miR-145 therefore opens new avenues on the factors that can affect epididymal functions that are essential for proper sperm maturation.…”

Section: Discussionmentioning

confidence: 71%

Role of MicroRNAs in Controlling Gene Expression in Different Segments of the Human Epididymis

et al. 2012

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BackgroundThe molecular mechanisms implicated in regionalized gene expression in the human epididymis have not yet been fully elucidated. Interestingly, more than 200 microRNAs (miRNAs) have been identified in the human epididymis and could be involved in the regulation of mRNA stability and post-transcriptional expression in this organ.MethodsUsing a miRNA microarray approach, we investigated the correlation between miRNA signatures and gene expression profiles found in three distinct regions (caput, corpus and cauda) of human epididymides from 3 donors. In silico prediction of transcript miRNA targets was performed using TargetScan and Miranda software's. FHCE1 immortalized epididymal cell lines were cotransfected with mimic microRNAs and plasmid constructs containing the 3′UTR of predicted target genes downstream of the luciferase gene.ResultsWe identified 35 miRNAs differentially expressed in the distinct segments of the epididymis (fold change ≥2, P-value≤0.01). Among these miRNAs, miR-890, miR-892a, miR-892b, miR-891a, miR-891b belonging to the same epididymis-enriched cluster located on the X chromosome, are significantly more expressed in the corpus and cauda regions than in the caput. Interestingly, a strong negative correlation (r = −0,89, P-value≤0.001) was found between the pattern of expression of miR-892b and its potential mRNA target Esrrg (Estrogen Related Receptor Gamma) and with miR-145 and Cldn10 mRNA (r = −0,92, P-value≤0.001). We confirmed that miR-145 and miR-892b inhibit the expression of the luciferase reporter via Cldn10 and Esrrg 3′ UTRs, respectively.ConclusionOur study shows that the expression of miRNAs is segmented along the human epididymis and correlates with the pattern of target gene expression in different regions. Therefore, epididymal miRNAs may be in control of the maintenance of gene expression profile in the epididymis, which dictates segment-specific secretion of proteins and establishes physiological compartments that directly or indirectly affect sperm maturation and fertility.

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“…A key component of epididymal physiology is the formation and maintenance of the blood‐epididymis barrier, which is critical for male fertility and requires coordinated function of the multiple cell types which comprise the epithelium (Cyr et al ., , ). Alterations to components of this barrier have been linked with infertility and, in more extreme cases, with the formation of sperm granulomas (Dube et al ., , ; Gregory & Cyr, ). Cell renewal is an essential function of all epithelia, especially of cells comprising tight junctions in cellular barriers.…”

Section: Introductionmentioning

confidence: 99%

Tissue regeneration and the epididymal stem cell

2019

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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. Figure 7 (A) 3D cell culture of dispersed single epididymal cells. Bright-field images of epididymal spheres and organoids differentiated under 3D culture in Matrigel and a commercial cell culture medium (Prostacult, Stem cell Technologies, Vancouver, BC) supplemented with EGF, bFGF, and heparin. After 2 days of culture, two types of structures of <100 lm can be seen: 1. structures with irregular shape and; 2. spheres with a smooth outline. These structures then become more regular and can reach or exceed 100 lm in diameter after 4-6 days in culture. Scale bar, 100 lm. (B) Immunolocalization of Cx43 in a typical organoid following 11 days of culture. Cx43 is normally expressed in basal cells, and is shown to localize in the cells at the base of the organoid thereby indicating cell sorting and self-organization of the organoid. ANDROLOGY

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Alterations in the Human Blood-Epididymis Barrier in Obstructive Azoospermia and the Development of Novel Epididymal Cell Lines from Infertile Men1

Cited by 26 publications

References 52 publications

Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

Role of MicroRNAs in Controlling Gene Expression in Different Segments of the Human Epididymis

Tissue regeneration and the epididymal stem cell

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