Small RNAs are trafficked from the epididymis to developing mammalian sperm
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ABSTRACT:
PROVIDER: PRJNA449691 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6984070.fastq.gz | Fastqsanger.gz | |||
| SRR6984080.fastq.gz | Fastqsanger.gz | |||
| SRR6984090.fastq.gz | Fastqsanger.gz | |||
| SRR6984100.fastq.gz | Fastqsanger.gz | |||
| SRR6984110.fastq.gz | Fastqsanger.gz |
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Project description:RNAs present in mature mammalian sperm are delivered to the zygote at fertilization, where they have the potential to affect early development. The biogenesis of the small RNA payload of mature sperm is therefore of great interest, as it may be a target of signaling pathways linking paternal conditions to offspring phenotype. Recent studies have suggested the surprising hypothesis that the small RNA payload carried by mature sperm may include RNAs that were not synthesized during testicular spermatogenesis, but that are instead delivered to sperm during the process of post-testicular maturation in the epididymis. To further test this hypothesis, we characterized small RNA dynamics during testicular and post-testicular germ cell maturation in mice, confirming and extending prior observations that testicular germ cell populations carry extremely low levels of tRNA fragments (tRFs), which only become highly abundant only after sperm have entered the epididymis. We examined the sperm RNA repertoire in greater detail, finding that the majority of 5’ tRNA fragments carry a 2’-3’ cyclic phosphate at their 3’ end, pointing to a role for RNaseA or T-family nucleases in tRNA cleavage in the male reproductive tract. The process of small RNA delivery to sperm can be recapitulated in vitro, as caput epididymosomes deliver small RNAs including tRFs and microRNAs to mature testicular spermatozoa. Finally, to definitively identify the tissue of origin for small RNAs in sperm, we carried out tissue-specific metabolic labeling of RNAs in intact mice, finding that mature sperm carry small RNAs that were originally synthesized in the somatic cells of the epididymis. Taken together, our data demonstrates that soma-germline small RNA transfer occurs in male mammals, most likely via vesicular transport from the epididymis to maturing sperm.
2018-07-15 | GSE112990 | GEO
Project description: Not available
| S-EPMC6103849 | biostudies-literature
Project description:The epididymis is an important component of the male reproductive system and a crucial site for sperm maturation. During the process of sperm maturation through the epididymis, the effective payload of SncRNA significantly changes, which may be related to epigenetic modifications. Unfortunately, the N6 Methyladenosine (m6A) modification profile of the epididymis has not yet been established. In this study, the MeRIP seq combined with RNA seq method was used to analyze the m6A modification levels in the head, body, and tail of yak epididymis. It was found that the level of m6A in the epididymis significantly increased, and differentially methylated RNAs (DMRs) in the proximal end of the epididymis were significantly enriched in Gap junction, ErbB signaling pathway, and mTOR signaling pathway, participating in cell communication and sperm maturation processes. In the distal epididymis, DMRs are enriched in Apoptosis, FoxO signaling pathway, PI3K Akt signaling pathway, and TNF signaling pathway, which are involved in sperm autophagy, oxidative stress, and sperm maturation. In addition, we identified key genes with significant changes in m6A levels but no differences in RNA levels, including YY1 associated factor 2 (YAF2), Fork head box J2 (FOXJ2), and Fork head box O1 (FOXO1), suggesting that these genes are modified by m6A to affect translation processes and participate in sperm maturation. In summary, our study established an m6A map of the epididymis, which is beneficial for further understanding the maturation process of sperm and revealing more information related to male infertility.
2024-06-01 | GSE264337 | GEO
Project description:The small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) vs. distal (cauda) epididymis, then characterized development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, and subsequently implant inefficiently and fail soon after implantation. Remarkably, microinjection of purified cauda-specific small RNAs into caput-derived embryos not only completely rescued preimplantation molecular defects, but also suppressed the postimplantation embryonic lethality phenotype. These findings reveal an essential role for small RNA remodeling during post-testicular maturation of mammalian sperm, and identify a specific preimplantation gene expression program responsive to sperm-delivered microRNAs.
2018-07-25 | GSE111864 | GEO
Project description:While mature sperm is transcriptionally inactive, recent studies show that, following testicular its exit, the mammalian sperm acquires a load of small non-coding RNAs during transit in the epididymis, the last stage of sperm maturation. Importantly, this non-coding RNA load is sensitive to environmental insults.
2023-06-01 | GSE221431 | 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: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:Spermatozoa harbor a complex and environment sensitive pool of small non-coding RNAs (sncRNA)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. We used two distinct paradigms of preconception acute high fat diet to dissect epididymal vs testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs and their fragments (mt-tsRNA) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with BMI and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA-seq of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that alterations of mt-tsRNAs are downstream of mitochondrial dysfunction. Most importantly, single embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilisation and implied them in the control of early embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, for the first time in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization. This SuperSeries is composed of the SubSeries listed below.
2024-04-03 | GSE239815 | GEO
Project description:The epididymis is comprised of multiple segments/compartments that, in addition to concentrating sperm and preventing their premature activation, play key roles in remodeling the protein, lipid, and RNA composition of maturing sperm. In order to understand the complex roles for the epididymis in reproductive biology, we generated a single cell atlas of gene expression from the murine epididymis and vas deferens using droplet-based (10X Chromium) single cell RNA-Seq. Following single-cell RNA-Seq, quality control, and removal of reads attributable to contaminating cell-free RNA we were able to profiled the expression of 16878 genes in 8,880 individual cells with an average of 3110 (median = 1965) unique molecular identifiers (UMIs) per cell from across the epididymis and the vas deferens. We recovered all the key cell types of the epididymal epithelium, including principal cells, clear cells, and basal cells, along with its associated support cells that include fibroblasts, smooth muscle, macrophages and other immune cells. Our data confirm and extend prior studies of segment-restricted gene expression programs, and reveal that these region-specific programs are largely driven by principal cells. In addition to the extensive region-specific specialization of principal cells, we find evidence for functionally-specialized subpopulations of stromal cells, and, most notably, two distinct populations of clear cells. Furthermore, we find several novel cell subpopulations, most notably including an Amylin-positive clear cell subtype, and predict intercellular signaling networks between the various cell types. Together, these data provide an atlas of cell composition across the epididymis, and a wealth of molecular hypotheses for future efforts in reproductive physiology.
2020-02-19 | GSE145443 | GEO
Project description:The three-dimensional (3D) organization of chromosomes is crucial for packaging a large mammalian genome into a confined nucleus and ensuring proper nuclear functions in somatic cells. However, the packaging of the much more condensed sperm genome is fundamentally different and not as well understood. In this study, we resolved the 3D whole-genome structures of a single mammalian sperm cell using an enhanced chromosome conformation capture assay. The reconstructed genome structures accurately delineate the species-specific nuclear morphologies for both human and mouse sperm. We discovered that sperm genomes are divided into chromosomal territories and A/B compartments, similarly as somatic cells. However, neither human nor mouse sperm chromosomes contain topologically associating domains or chromatin loops. These results suggest that the fine-scale chromosomal organization of mammalian sperm fundamentally differs from that of somatic cells.
2025-03-09 | GSE277016 | GEO