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Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model

ABSTRACT: Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model

PROVIDER: PRJNA915125 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22873700_1.fastq.gz	Fastqsanger.gz
	SRR22873700_2.fastq.gz	Fastqsanger.gz
	SRR22873701_1.fastq.gz	Fastqsanger.gz
	SRR22873701_2.fastq.gz	Fastqsanger.gz
	SRR22873702_1.fastq.gz	Fastqsanger.gz

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

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

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

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

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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

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

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

| PRJNA914294 | ENA

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

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

Sperm DNA Methylation Epimutation Biomarker for Paternal Offspring Autism Susceptibility

Project description:Autism spectrum disorder (ASD) has increased over ten-fold over the past several decades, and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now thought to be an important factor. Epigenetic alterations, such as DNA methylation have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility. Sperm samples were obtained from fathers, many undergoing in vitro fertilization (IVF) procedures, that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. Differential DNA methylation regions (DMRs) were identified in the sperm of fathers with autistic children in comparison to those without ASD children. An MeDIP-seq procedure was used to identify DMRs. The genomic features and genes associated with the DMRs were identified. The potential sperm DMR biomarker was validated with a blinded test set of individuals. Observations demonstrate a significant set of DMRs in sperm can potentially act as a biomarker for paternal offspring autism susceptibility.

2020-12-01 | GSE157417 | GEO

Sperm DNA Methylation Epimutation Biomarker for Paternal Offspring Autism Susceptibility

Project description:Sperm DNA Methylation Epimutation Biomarker for Paternal Offspring Autism Susceptibility

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Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-01 | GSE221649 | GEO

Sperm transcriptional state associated with paternal transmission of stress phenotypes

Project description:Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and -susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation. We demonstrate differences in offspring from stressed fathers that depend upon paternal category (resilient vs susceptible) and offspring sex. Importantly, artificial insemination reveals that sperm mediates some of the behavioral phenotypes seen in offspring. Using RNA-sequencing we report substantial and distinct changes in the transcriptomic profiles of sperm following CSDS in susceptible vs resilient fathers, with alterations in long noncoding RNAs (lncRNAs) predominating especially in susceptibility. Correlation analysis revealed that these alterations were accompanied by a loss of regulation of protein-coding genes by lncRNAs in sperm of susceptible males. We also identify several co-expression gene modules that are enriched in differentially expressed genes in sperm from either resilient or susceptible fathers. Taken together, these studies advance our understanding of intergenerational epigenetic transmission of behavioral experience.

2024-05-20 | GSE174780 | GEO

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