Epididymosomes convey different repertoires of miRNAs throughout the epididymis
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ABSTRACT:
ORGANISM(S): synthetic construct Bos taurus
PROVIDER: GSE44365 | GEO | 2013/07/01
SECONDARY ACCESSION(S): PRJNA189565
REPOSITORIES: GEO
Similar Datasets
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:Between the testes and the vas deferens lies the epididymis, a highly convoluted tubule whose unique environmental characteristics are crucial for the functional maturation of spermatozoa. Within the epididymal epithelium, the secretory system releases small non-coding RNA molecules (sncRNAs) and proteins housed within extracellular vesicles (epididymosomes) that are destined for delivery to recipient sperm cells which play key roles in fertility success and act as major conduits of epigenetic information delivered to the oocyte. The epithelial cells of the epididymis have proven to be highly sensitive to environmental stressors which can influence the sperm epigenome. Utilizing a label-free mass spectrometry proteomic approach we sought to characterize an immortalized mouse caput epididymal epithelial cell line (mECap18) and sequenced >5,100 proteins. When compared to a previous in-vivo mouse caput epithelial proteomic profile, a significant overlap (>75%) and proportionally similar patterns of protein classification were observed. Furthermore, key pathways associated with protein synthesis (e.g. EIF2 signaling) and cellular protection in the male reproductive tract (e.g. sirtuin signaling) were enriched in both proteomes. Leveraging this comparison supports mECap18 cells as a promising in-vitro model for recapitulating the in-vivo environment, providing a platform for testing therapeutic invention.
2023-09-29 | PXD042082 | Pride
Project description:Interest in the sperm epigenome continues to grow in view of the realization that it is vulnerable to dynamic modifications arising from a variety of paternal environment exposures and that this legacy can serve as an important determinant of intergenerational inheritance. It has been postulated that such exchange may be communicated to maturing populations of spermatozoa via the transfer of small non-coding RNAs in a mechanism involving epididymosomes; small membrane bound vesicles secreted by the soma of the male reproductive tract (epididymis). Herein we confirm that mouse epididymosomes encapsulate an impressive repertoire of >350 microRNA (miRNA), a majority (~60%) of which are also represented in the miRNA signature of maturing spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma, thus supporting the notion that epididymosomes may selectively deliver regulatory non-coding RNA cargo to maturing sperm. Interestingly, we also documented substantial plasticity in terms of the epididymosome-borne miRNAs, including significant fold changes in the relative abundance of almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNAs between mouse epididymosomes and spermatozoa, and in so doing afford novel insight into a mechanism of intercellular communication through which the RNA payload of sperm can be modified during their post-testicular development. Examination of the microRNA expression profile of mouse epididymal epididymosomes using next generation sequencing in triplicate.
2016-08-25 | E-GEOD-79500 | biostudies-arrayexpress
Project description:Interest in the sperm epigenome continues to grow in view of the realization that it is vulnerable to dynamic modifications arising from a variety of paternal environment exposures and that this legacy can serve as an important determinant of intergenerational inheritance. It has been postulated that such exchange may be communicated to maturing populations of spermatozoa via the transfer of small non-coding RNAs in a mechanism involving epididymosomes; small membrane bound vesicles secreted by the soma of the male reproductive tract (epididymis). Herein we confirm that mouse epididymosomes encapsulate an impressive repertoire of >350 microRNA (miRNA), a majority (~60%) of which are also represented in the miRNA signature of maturing spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma, thus supporting the notion that epididymosomes may selectively deliver regulatory non-coding RNA cargo to maturing sperm. Interestingly, we also documented substantial plasticity in terms of the epididymosome-borne miRNAs, including significant fold changes in the relative abundance of almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNAs between mouse epididymosomes and spermatozoa, and in so doing afford novel insight into a mechanism of intercellular communication through which the RNA payload of sperm can be modified during their post-testicular development.
2016-08-25 | GSE79500 | GEO
Project description:BACKGROUND: Vasectomized men who wish for restoration of fertility commonly face problems to conceive despite high surgical success rates of vasovasostomy, a surgery routinely used to retrieve duct patency. In human, vasectomy has consequences on the epididymal transcriptome and is responsible for non-reversible changes that affect the biochemical parameters and functions of ejaculated sperm in vasovasotomized men. Since microRNAs (miRNAs) are key regulators of post-transcriptional gene expression, we explored the consequences of vasectomy on miRNA pattern in the human epididymis and determined the repercussion and reversibility of these changes in seminal microvesicles (SMVs) from semen of vasovasostomized men. METHOD: miRNA signatures from a unique set of human epididymal segments (caput, corpus, cauda) provided by controls and vasectomized donors as well as miRNA content of SMVs isolated from semen of normal, vasectomized and vasovasostomized donors were determined by using high-throughput microarray technology. Epididymal miRNA signature was correlated with gene expression profiles by employing an integrated genomic approach. RESULTS: While the segmented pattern of miRNA expression was maintained along the human epididymis following vasectomy, the array of miRNAs from each anatomical region significantly differed between normal and vasectomized donors. Greatest changes were observed in cauda epididymidis and were negatively correlated with transcription factors. Vasectomy also impacted expression of miRNAs found in SMVs from normal donors, including miRNAs of epididymal origin contained in epididymosomes. Among seminal miRNAs sequelae, 52 were reversible according to miRNA expression level following duct patency retrieval. In contrast, 66 of miRNAs found in SMVs were not retrieved in SMVs after vasovasostomy. CONCLUSION: We showed that vasectomy has a substantial impact on the miRNA signature of the epididymis and SMVs, and that vasovasostomy does not restore all molecular players found in normal fertile individuals. According to the critical role played by miRNAs in the control of male fertility, we believe that miRNA sequelae occurring upstream and downstream of the vasectomy site may be in part responsible for the reduced fertility outcome reported after surgically successful vasectomy reversal. Human epididymides from 3 control (26, 47 and 50 years old. GEO accession number GSE35522) and 3 vasectomized donors (45, 47 and 48 years old), were collected and dissected into 3 anatomical regions (caput, corpus and cauda). Seminal microvesicles (SMVs) were isolated from the semen of normal (pool of 3 donnors), vasectomized (pool of 3 donnors) and vasovasostomized donors (pool of 5 donnors). A cross-comparison between the miRNA signature found in different segments and seminal vesicles was performed using GeneChip miRNA Array 2.0 (Affimetrix, Santa Clara, CA).
2013-02-25 | E-GEOD-43676 | biostudies-arrayexpress
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: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:BACKGROUND: Vasectomized men who wish for restoration of fertility commonly face problems to conceive despite high surgical success rates of vasovasostomy, a surgery routinely used to retrieve duct patency. In human, vasectomy has consequences on the epididymal transcriptome and is responsible for non-reversible changes that affect the biochemical parameters and functions of ejaculated sperm in vasovasotomized men. Since microRNAs (miRNAs) are key regulators of post-transcriptional gene expression, we explored the consequences of vasectomy on miRNA pattern in the human epididymis and determined the repercussion and reversibility of these changes in seminal microvesicles (SMVs) from semen of vasovasostomized men. METHOD: miRNA signatures from a unique set of human epididymal segments (caput, corpus, cauda) provided by controls and vasectomized donors as well as miRNA content of SMVs isolated from semen of normal, vasectomized and vasovasostomized donors were determined by using high-throughput microarray technology. Epididymal miRNA signature was correlated with gene expression profiles by employing an integrated genomic approach. RESULTS: While the segmented pattern of miRNA expression was maintained along the human epididymis following vasectomy, the array of miRNAs from each anatomical region significantly differed between normal and vasectomized donors. Greatest changes were observed in cauda epididymidis and were negatively correlated with transcription factors. Vasectomy also impacted expression of miRNAs found in SMVs from normal donors, including miRNAs of epididymal origin contained in epididymosomes. Among seminal miRNAs sequelae, 52 were reversible according to miRNA expression level following duct patency retrieval. In contrast, 66 of miRNAs found in SMVs were not retrieved in SMVs after vasovasostomy. CONCLUSION: We showed that vasectomy has a substantial impact on the miRNA signature of the epididymis and SMVs, and that vasovasostomy does not restore all molecular players found in normal fertile individuals. According to the critical role played by miRNAs in the control of male fertility, we believe that miRNA sequelae occurring upstream and downstream of the vasectomy site may be in part responsible for the reduced fertility outcome reported after surgically successful vasectomy reversal.
2013-02-25 | GSE43676 | GEO
Project description:Previously the agricultural fungicide vinclozolin was found to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs) termed epimutations that help mediate this epigenetic inheritance. The current study was designed to investigate the developmental origins of the transgenerational DMRs during gametogenesis. Male control and vinclozolin lineage F3 generation rats were used as a source of embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, and adult pachytene spermatocytes, round spermatids, caput epididymal sperm, and caudal sperm. The DMRs between the control versus vinclozolin lineage samples were determined for each developmental stage. The top 100 statistically significant DMRs for each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed.
2018-11-01 | GSE117995 | GEO
Project description:It has been demonstrated that males exposed to adversity prior to conception sire offspring exhibiting abnormal behaviour and neuroendocrine function. Epigenetic factors such as microRNA (miRNA) within sperm may be responsible for driving these effects. Synthetic glucocorticoids (sGC) are a class of drug that are commonly prescribed and may have implications for intergenerational transmission. Therefore, we hypothesized that caput and cauda sperm miRNA profiles will be altered following sGC exposure in guinea pigs. We used miRNA microarray to evaluate the miRNA levels of caput and cauda sperm isolated from guinea pigs exposed to control and water treated with sGC. We identified a subset of miRNAs with low levels in cauda sperm of guinea pigs exposed to sGC.
2023-03-17 | GSE226168 | GEO