The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE208244 | GEO | 2022/11/30
REPOSITORIES: GEO
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Project description:Epididymosomes are small membrane vesicles (50-500nm) secreted by epididymal epithelial cells and involved in post-testicular sperm maturation. While their role in protein transfer to the sperm membrane is well acknowledged, we unveil here their capacity to vehicle microRNAs (miRNAs), which are potent regulators of post-transcriptional gene expression. Using a global microarray approach, we showed that epididymosomes providing from two discrete bovine epididymal regions (caput and cauda) possess distinct miRNA signatures. In addition, we established that miRNA repertoires contained in epididymosomes differ from those of their parent epithelial cells, suggesting that miRNA populations released from the cells may be selectively sorted. Binding of DilC12-labeled epididymosomes to primary cultured epididymal cells was measured by flow cytometry and indicated that epididymosomes from the median caput and their miRNA content may be incorporated into distal caput epithelial cells. Overall, these findings reveal that distinct miRNA repertoires are released into the intraluminal fluid in a region-specific manner and could be involved in a novel mechanism of intercellular communication throughout the epididymis via epididymosomes. We determined the miRNA profiles of epididymosomes isolated by perfusion from caput and cauda regions of the epididymis and compared it with the miRNA content of epididymal epithelial cells from the same regions.
2013-07-01 | E-GEOD-44365 | biostudies-arrayexpress
Project description:Epididymosomes are small membrane vesicles (50-500nm) secreted by epididymal epithelial cells and involved in post-testicular sperm maturation. While their role in protein transfer to the sperm membrane is well acknowledged, we unveil here their capacity to vehicle microRNAs (miRNAs), which are potent regulators of post-transcriptional gene expression. Using a global microarray approach, we showed that epididymosomes providing from two discrete bovine epididymal regions (caput and cauda) possess distinct miRNA signatures. In addition, we established that miRNA repertoires contained in epididymosomes differ from those of their parent epithelial cells, suggesting that miRNA populations released from the cells may be selectively sorted. Binding of DilC12-labeled epididymosomes to primary cultured epididymal cells was measured by flow cytometry and indicated that epididymosomes from the median caput and their miRNA content may be incorporated into distal caput epithelial cells. Overall, these findings reveal that distinct miRNA repertoires are released into the intraluminal fluid in a region-specific manner and could be involved in a novel mechanism of intercellular communication throughout the epididymis via epididymosomes.
2013-07-01 | GSE44365 | GEO
Project description:Mammalian spermatozoa acquire their fertilizing ability during epididymal transit. Gene expression patterns along the epididymis are established by specific transcription factor networks that coordinate region-specific functions. The epididymis is usually divided into 3 segments: caput, corpus, and cauda. The human epididymis anatomy does not allow clear distinction between these three segments. To determine to which extent gene expression is segmented along the human epididymis, transcriptome profiling was performed on 8 distinct epididymal regions from 3 donors. Microarray analysis was performed on a Gene Chip Human Clariom S (Affymetrix®) array representing 337 100 transcriptional variants encoded by 20 800 genes. Proximal segments 1 to 3 were distinguishable from the distal epididymal segments (4 to 8) as shown by unsupervised Principal Component Analysis. Transcripts from each segment with differentially expressed genes (DEGs) > 2-fold change and FDR < 0.05 were clustered in relation to their intensity profiles. While no DEGs were detected between segments 1–3 corresponding to the efferent ducts, 1140 DEGs were detected between efferent ducts (1–3) and the epididymis (4–8), 400 between caput (4–6) vs. corpus/cauda (7–8) and none between corpus (7) and cauda (8). Gene Ontology annotation revealed that up-regulated DEGs in the efferent ducts (1–3) were predominantly related to cilium assembly/movement and cell differentiation. The biological process terms fertilization, defense and immune responses were associated with caput epididymis (4–6) while spermatogenesis and protein binding were found all along the epididymis (4–8). In conclusion, the proximal human epididymis is exclusively occupied by efferent ducts with a distinct DEG profile compared with the downstream epididymal segments. Moreover, gene expression profiling revealed two regions in the human epididymis; the caput and the distal corpus/cauda region. Taken together, analysis of the human epididymal transcriptome reveals a limited DEG profile.
2020-11-06 | GSE141568 | GEO
Project description:Worldwide, almost 100 millions men rely on vasectomy for male contraceptive purposes. Due to changes in their personal life, an increasing number of these men request surgical vasectomy reversal. Unfortunately, a significant proportion of these men remain infertile, despite the reestablishment of patent ducts, possibly due to epididymal damages caused by vasectomy. In animal models, vasectomy affects different epididymal physiological and biochemical parameters. However, consequences of vasectomy on these biochemical parameters are poorly understood at the molecular level. Furthermore, results obtained with animal models cannot by extrapolated to human to understand the consequences of vasectomy on epididymal functions. Gene expression pattern of epididimydis is highly regulated. We previously showed that the human epididymal expression pattern of two genes is altered under vasectomy. To complete the list of epididymal genes affected by vasectomy, we analysed the epididymal gene expression profile of three vasectomised donors, using the affymetrix human GeneChip U133 Plus 2. These results were compared with gene expression pattern of three ânormalâ donors. The data generated allowed the identification of many human epididymal genes for which the expression is modified under vasectomy. Qt-PCR and western-blot analysis of six selected genes known to be expressed in specific epididymal segments were performed. The Qt-PCR results confirmed the selected transcripts expression pattern deduced from microarrays data, while the western-blot analysis revealed some differences in protein distribution along the epididymis when compared to the transcripts expression pattern. These results contribute to the understanding of the causes of the persistent of infertility even though spermogram values suggest surgical success of vasovasostomy. Experiment Overall Design: Vasectomised epididimus, corpus caput and cauda segments
2008-10-25 | E-GEOD-9731 | biostudies-arrayexpress
Project description:Worldwide, almost 100 millions men rely on vasectomy for male contraceptive purposes. Due to changes in their personal life, an increasing number of these men request surgical vasectomy reversal. Unfortunately, a significant proportion of these men remain infertile, despite the reestablishment of patent ducts, possibly due to epididymal damages caused by vasectomy. In animal models, vasectomy affects different epididymal physiological and biochemical parameters. However, consequences of vasectomy on these biochemical parameters are poorly understood at the molecular level. Furthermore, results obtained with animal models cannot by extrapolated to human to understand the consequences of vasectomy on epididymal functions. Gene expression pattern of epididimydis is highly regulated. We previously showed that the human epididymal expression pattern of two genes is altered under vasectomy. To complete the list of epididymal genes affected by vasectomy, we analysed the epididymal gene expression profile of three vasectomised donors, using the affymetrix human GeneChip U133 Plus 2. These results were compared with gene expression pattern of three “normal” donors. The data generated allowed the identification of many human epididymal genes for which the expression is modified under vasectomy. Qt-PCR and western-blot analysis of six selected genes known to be expressed in specific epididymal segments were performed. The Qt-PCR results confirmed the selected transcripts expression pattern deduced from microarrays data, while the western-blot analysis revealed some differences in protein distribution along the epididymis when compared to the transcripts expression pattern. These results contribute to the understanding of the causes of the persistent of infertility even though spermogram values suggest surgical success of vasovasostomy. Keywords: Tissue compartments comparison
2008-09-22 | GSE9731 | GEO
Project description:Study question: Can region-specific transcriptional profiling of the epididymis from fertile and sub-fertile bulls predict the aetiology of fertility/subfertility in males? Summary answer:The highly regulated gene expression along the bovine epididymis is affected by the fertility status of bulls used for artificial insemination. What is known already: In mammals, sperm maturation and storage occur in the epididymis. Each epididymal segment has his own transcriptomic signature that modulates the intraluminal composition that governs sequential modifications of the maturing male gamete. Main results and the role of chance: Hierarchical clustering and Principal Component Analysis revealed a clear separation between caput, corpus and cauda epididymides. Some transcripts characterize a particular anatomical segment, whereas others are expressed in two out of three epididymal segments. GO analysis allowed deduction of specific functions played by each epididymal segment. The transcriptional profiles between fertile vs. sub-fertile conditions clustered most closely in the corpus and cauda segments, whereas the profiles in the caput segment were distinct between fertile and sub-fertile bulls. Of the differently expressed genes, ten (including AKAP4, SMCP, SPATA3, TCP11, ODF1, CTCFL, SPATA18, ADAM28, SORD and FAM161A) were found to exert functions related to reproductive systems and 5 genes (including DEAD, CYST11, DEFB119, DEFB124 and MX1) were found to be associated with the defence response. Limitations, reasons for caution: Further work is required to correlate these modulations of epididymal functions with sperm fertilizing ability in order to understand the aetiology of certain cases of idiopathic infertility in livestock and men. Wider implications of the findings: As fertility can be quantified in bulls used for artificial insemination, this species is a unique model to aid in the understanding of male fertility/subfertility in man.Our data provide a molecular characterization that will facilitate advances in understanding the involvement of epididymalphysiology in sub/infertility aetiology.
2017-03-31 | GSE96602 | GEO
Project description:The epididymis can be subdivided into three regions, the caput, corpus and cauda epididymidis, that have different characteristics and functions. Goal was to determine the differential pattern of gene expression along the regions of the human epididymis. Two-condition experiment, region 1 vs region 2. Replicates: 4 biological replicates from each epididymal region.
2010-08-25 | E-GEOD-23812 | biostudies-arrayexpress
Project description:Following their production in the testis, spermatozoa enter the epididymis to gain their motility and fertilizing abilities. This post-testicular maturation coincides with sperm epigenetic profile changes that influence the progeny outcome. While recent studies underscored the dynamics of small non-coding RNAs in the maturing spermatozoa, little is known regarding sperm methylation changes and their impact at the post-fertilization level. To map out the sperm methylome dynamics, we purified spermatozoa by FACS from the testis and the different epididymal segments (i.e. caput, corpus and cauda) of CAG/su9-DsRed2; Acr3-EGFP transgenic mice. Reduced-Representation Bisulfite Sequencing (RRBS-Seq) performed on DNA from these respective sperm populations indicated that high methylation changes were observed between spermatozoa from the caput vs. testis with 5546 entries meeting our threshold values (q value < 0.01, methylation difference above 25 %). Most of these changes were transitory during epididymal sperm maturation according to the low number of entries identified between spermatozoa from cauda vs. testis.
2022-03-10 | GSE191051 | GEO
Project description:The epididymis exhibits a less restrictive physical blood-tissue barrier than the testis and, while numerous immunosuppressive factors have been identified in the latter, no mechanisms for epididymal immunotolerance have been identified to date. Therefore, data are currently insufficient to explain how the immune system tolerates the extremely large load of novel antigens expressed on sperm, which become present in the male body after puberty, i.e. long after central tolerance was established. This study tested the hypothesis that TGFβ-signaling in dendritic cells (DCs) is required for immunotolerance to sperm located in the epididymis, and that male mice lacking TGFβ-signaling in DCs would develop severe epididymal inflammation. To test this, we employed adult Tgfbr2ΔDC males, which exhibit a significant reduction of Tgfbr2 expression and TGFβ-signaling in DCs, as reported previously. Results show that Tgfbr2ΔDC males exhibit sperm-specific immune response and severe epididymal leukocytosis. This phenotype is consistent with epididymal loss of immunotolerance to sperm, and suggests that TGFβ-signaling in DCs is a factor required for a non-inflammatory steady state in the epididymis, and therefore for male tract homeostasis and function.
2018-08-08 | GSE118262 | GEO
Project description:The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment is, in turn, created by the combined secretory and absorptive activity of the surrounding epithelium and displays an extraordinary level of regionalization. Although the regulatory network responsible for spatial coordination of epididymal function remains unclear, recent evidence has highlighted a novel role for the RNA interference pathway. Indeed, as noncanonical regulators of gene expression, small noncoding RNAs have emerged as key elements of the circuitry involved in regulating epididymal function and hence sperm maturation. Herein we have employed next generation sequencing technology to profile the genome-wide miRNA signatures of mouse epididymal cells and characterize segmental patterns of expression. An impressive profile of some 370 miRNAs were detected in the mouse epididymis, with a subset of these specifically identified within the epithelial cells that line the tubule (218). A majority of the latter miRNAs (75%) were detected at equivalent levels along the entire length of the mouse epididymis. We did however identify a small cohort of miRNAs that displayed highly regionalized patterns of expression, including miR-204-5p and miR-196b-5p, which were down- and up-regulated by approximately 39- and 45-fold between the caput/caudal regions, respectively. In addition we identified 79 miRNAs (representing ~ 21% of all miRNAs) as displaying conserved expression within all regions of the mouse, rat and human epididymal tissue. These included 8/14 members of let-7 family of miRNAs that have been widely implicated in the control of androgen signaling and the repression of cell proliferation and oncogenic pathways. Overall these data provide novel insights into the sophistication of the miRNA network that regulates the function of the male reproductive tract. Examination of the microRNA expression profile in the whole mouse epididymis and mouse epididymal epithelial cells using next generation sequencing in duplicate.
2015-07-29 | E-GEOD-70197 | biostudies-arrayexpress