Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE221630 | GEO | 2023/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

Project description:DNA sequence accounts for the majority of disease heritability, including cancer. Yet, not all familial cancer cases can be explained by genetic factors. It is becoming clear that environmentally induced epigenetic inheritance occurs and that the progeny’s traits can be shaped by parental environmental experiences. In humans, epidemiological studies have implicated environmental toxicants, such as the pesticide DDT, in intergenerational cancer development, including breast and childhood tumors. Here, we show that the female progeny of males exposed to DDT in the pre-conception period have higher susceptibility to developing aggressive tumors in mouse models of breast cancer. Sperm of DDT-exposed males exhibited distinct patterns of small non-coding RNAs, with an increase in miRNAs and a specific surge in miRNA-10b levels. Remarkably, embryonic injection of the entire sperm RNA load of DDT-exposed males, or synthetic miRNA-10b, recapitulated the tumor phenotypes observed in DDT offspring. Mechanistically, miR-10b injection altered the transcriptional profile in early embryos with enrichment of genes associated with cell differentiation, tissue and immune system development. In adult DDT-derived progeny, transcriptional and protein analysis of mammary tumors revealed alterations in stromal and in immune system compartments. Our findings reveal a causal role for sperm RNAs in environmentally induced inheritance of cancer predisposition and, if confirmed in humans, this could help partially explain some of the “missing heritability” of breast, and other, malignancies.

2023-06-01 | GSE222357 | GEO

Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment

Project description:We report reproductive tract extracellular vesicles (EVs) transmit information regarding stress in the paternal environment to sperm, ultimately altering fetal development. Using intracytoplasmic sperm injection, we found that sperm incubated with EVs collected from stress-treated epididymal epithelial cells produced offspring with altered neurodevelopment and adult stress reactivity. Proteomic and transcriptomic assessment of these EVs showed dramatic changes in protein and miRNA content long after stress treatment had ended.

2020-02-11 | GSE145051 | GEO

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

Epigenetic Transgenerational Inheritance of Parent-of-Origin Allelic Transmission of Outcross Pathology and Sperm Epimutations Following Ancestral Toxicant Exposures

Project description:Previous observations have demonstrated that the agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) induce transgenerational sperm epimutations involving DNA methylation. These two environmental toxicants were used to investigate the impacts of parent-of-origin outcross on the epigenetic transgenerational inheritance of disease. Male and female rats were collected from a paternal outcross (POC) or a maternal outcross (MOC) F4 generation control and exposure lineages for pathology and epigenetic analysis. This model allows the parental allelic transmission of disease and epimutations to be investigated. There was increased pathology incidence in MOC outcross F4 generation male prostate, kidney, obesity and multiple diseases through a maternal allelic transmission. The POC outcross F4 generation female offspring had increase pathology incidence for kidney, obesity and multiple diseases through the paternal allelic transmission. Some disease such as testis or ovarian pathology appear to be transmitted through the combined actions of both male and female alleles. Analysis of the F4 generation sperm epigenomes identified differential DNA methylated regions (DMRs) in a genome-wide analysis. Observations demonstrate that DDT and vinclozolin have the potential to promote the epigenetic transgenerational inheritance of disease and sperm epimutations to the outcross F4 generation in a sex specific and exposure specific manner.

2019-07-23 | GSE130258 | GEO

Alterations in Sperm DNA Methylation, Non-coding RNA and Histone Retention Associate with DDT Induced Epigenetic Transgenerational Inheritance of Disease

Project description:Environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease through the germline. This study was designed to investigate DDT induced concurrent alterations of a number of different epigenetic processes including DNA methylation and histone retention in sperm. Gestating female rats were exposed transiently to DDT during fetal gonadal development and then F1, F2 and F3 generation sperm were analyzed.

2018-04-27 | GSE109775 | GEO

Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral DDT Exposure

Project description:In previous studies, the pesticide DDT was shown to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs), also called epimutations, which can mediate this epigenetic inheritance. In the current study, the developmental origins of the transgenerational DMRs during gametogenesis have been investigated. Male control and DDT lineage F3 generation rats were used to isolate embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus DDT lineage samples were determined at each developmental stage. The top 100 statistically significant DMRs at each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed.

2019-01-19 | GSE121585 | GEO

Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals (smallRNA-seq)

Project description:Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5â fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes â extracellular vesicles which fuse with sperm during epididymal transit â exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Small RNA (<40nt) profile of various tissues and cells was examined by deep sequencing

2015-12-31 | E-GEOD-75613 | biostudies-arrayexpress

Sperm Epimutation Biomarkers of Obesity and Pathologies following DDT Induced Epigenetic Transgenerational Inheritance of Disease

Project description:Gestating F0 generational female rats were transiently exposed to DDT during fetal gonadal sex determination and the incidence of adult onset pathologies was assessed in the subsequent F1, F2, and F3 generations. In addition, sperm differential DNA methylation regions (DMRs) that were associated with specific pathologies in the F3 generation males were investigated. No pathology was observed in the F1 generation DDT lineage males or females compared with F1 generation controls (vehicle exposure). There was an increase of testis disease and early onset puberty in the F2 generation DDT lineage males. The F3 generation DDT males had significant increases in testis disease, prostate disease, and late onset puberty. The F3 generation DDT females had significant increases in ovarian and kidney disease. Both the F3 generation males and females had significant increases in the frequency of obesity and multiple disease. The F3 generation sperm was collected to examine DMRs for the ancestrally exposed DDT male population. Unique sets of DMRs were associated with late onset puberty, kidney disease, and multiple disease pathologies.

2018-07-31 | GSE114032 | GEO

Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals (ICSI)

Project description:Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5â fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes â extracellular vesicles which fuse with sperm during epididymal transit â exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Zygotes were generated by ICSI from oocytes/females fed a Control diet and sperm/males fed either a Control or Low Protein diet. The sperm was isolated from either the Rete testis or the Cauda epididymis and injected either as a whole sperm or just the sperm head. Following fertilization by ICSI the zygotes developed for 28 hours (2C stage) and were harvested for single-embryo RNA-Seq.

2015-12-31 | E-GEOD-75769 | biostudies-arrayexpress

Developmental Origins of Transgenerational Sperm Histone Retention Following Ancestral Exposures

Project description:This study was designed to investigate the developmental origins of the transgenerational differential histone retention sites (called DHRs) during gametogenesis of the sperm. Vinclozolin and DDT were independently used to promote the epigenetic transgenerational inheritance of these DHRs. Male control, DDT lineage and vinclozolin lineage F3 generation rats were used to isolate round spermatids, caput epididymal spermatozoa, and caudal sperm. The DHRs between the control versus DDT lineage or vinclozolin lineage were determined in these three developmental stages. DHRs and a reproducible core of histone H3 retention sites were observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in the germ cell populations. The chromosomal locations and genomic features of the DHRs were also analyzed. A cascade of epigenetic histone retention site alterations was found to be initiated in or prior to the round spermatids that is further altered during epididymal sperm maturation. Observations show that in addition to alterations in sperm DNA methylation previously identified, the induction of differential histone retention sites (DHRs) in the later stages of spermatogenesis also occurs.

2019-12-31 | GSE137963 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data