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Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice

ABSTRACT: Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice

PROVIDER: PRJNA438441 | ENA |

REPOSITORIES: ENA

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Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice

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

Epididymal acquired sperm microRNAs modify post-fertilization embryonic gene expression

Project description:Sperm small RNAs have emerged as important non-genetic contributors to embryogenesis and offspring health. A subset of sperm small RNAs are thought to be acquired during epididymal transit. However, the transfer of RNAs from the somatic epididymis to the sperm has been questioned, and the identity of the specific small RNAs transferred remains unclear. Here, we employ Cre/Lox genetics to generate germline- and epididymal-specific Dgcr8 conditional knockout mice to investigate the dynamics of sperm microRNAs and their function in the early embryo. Interestingly, sperm from germline specific Dgcr8 knockout males restored the levels of 58 of the 98 (59%) miRNAs that were lost in testicular sperm during epididymal transit. Conversely, sperm from epididymal Dgcr8 knockouts displayed a 5-fold reduction in 25 miRNAs. This substantial loss of epididymal miRNAs in sperm was accompanied by transcriptomic changes in the embryo which was rescued by microinjection of epididymal miRNAs. These findings ultimately demonstrate the acquisition of miRNAs by sperm during epididymal transit and their regulation of post-fertilization embryonic gene expression.

2024-08-31 | GSE244885 | GEO

Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice.

Project description: Not available

| S-EPMC6103825 | biostudies-literature

Differential proteome between ejaculate and epididymal sperm represents a key factor for sperm freezability in wild small ruminants

Project description:The proteome of two sperm sources, epididymal and ejaculated sperm, was compared and associated with sperm freezing capacity using samples collected from three wild small ruminants species. Protein identification was performed using two databases separately (Ovis aries and Capra hircus NCBI) and results were later combined.

2021-05-04 | PXD017462 | Pride

Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model [RNA-seq]

Project description:Our study revealed that miRNAs constituted the main small RNA subtype altered by DDT exposure, with a specific DDT-induced surge in sperm miRNA-10b. This miRNA, along with other members of the miRNA-10 family, plays a critical role in embryonic development and cell differentiation through the regulation of Homeobox (Hox) and other genes. Interestingly, studies examining different paternal environmental exposures including obesity and malnutrition report a upregulation of miRNA-10b and other members of the miR-10 family in sperm. It has also been reported that both sperm miRNA-10a and miRNA-10b are conserved across species including humans. These miRNAs are acquired by sperm cells during epididymal transit in mice, suggesting that alterations in this family could potentially act as a “sensor” of paternal environments.

2023-06-01 | GSE221630 | GEO

Prm2 deficiency triggers a Reactive Oxygen Species (ROS)-mediated destruction cascade during epididymal sperm maturation in mice

Project description:Protamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Prm2-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm`s antioxidant capacity, indicated by downregulation of key proteins like SOD1 and PRDX5, ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.

2020-07-29 | GSE149454 | GEO

cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit.

Project description: Not available

| S-EPMC3424100 | biostudies-literature

TRANSIT

Project description:TRANSIT

| PRJEB39096 | ENA

Cabs1 Maintains Structural Integrity of Mouse Sperm Flagella during Epididymal Transit of Sperm.

Project description: Not available

| S-EPMC7827751 | biostudies-literature

Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model [non-coding RNA-Seq]

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

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