Transgenerational inheritance of chronic adolescent stress: Effects of stress response and the amygdala transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA427314 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6491660.fastq.gz | Fastqsanger.gz | |||
| SRR6491670.fastq.gz | Fastqsanger.gz | |||
| SRR6491661.fastq.gz | Fastqsanger.gz | |||
| SRR6491671.fastq.gz | Fastqsanger.gz | |||
| SRR6491662.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To begin to unravel the molecular mechanisms underlying these long-term effects, we determined if stress administered to males during adolescence (F0) altered anxiety behaviors and gene expression profiles in the amygdala – a critical region in the control of emotional states – of their progeny in two generations (F1, F2). Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for two-weeks during adolescence and were used to produce two generations of offspring. Male and female F1 and F2 animals were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. In behaviorally naïve mice (n = 5), mRNA from the amygdala was sequenced to determine the total transcriptomes and pathway analysis was employed to identify differentially expressed genes of functional interest. RNA-Seq analysis of the amygdala from F1 and F2 male offspring identified genes with altered expression in mice derived from fathers exposed to CUS. Among the differentially expressed pathway was ‘notch signaling’, which was significantly altered in F2 males. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.
2018-12-19 | GSE108452 | GEO
Project description:Stress Resets Transgenerational Small RNA Inheritance
| PRJNA533340 | ENA
Project description:Transgenerational inheritance is challenging basic concepts of heredity and achieving control over such responses is of great interest. In C. elegans nematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments. Inheritance of small RNAs is regulated by dedicated machinery and can be tuned by outside cues. Carryover of aberrant heritable small RNA responses was shown to be maladaptive and to induce sterility in certain cases. Here we show that various types of stress (starvation, high temperatures, and hyperosmotic conditions) but not non-stressful changes in cultivation, lead to resetting of small RNA inheritance. We found that stress leads to a genome-wide reduction in heritable small RNA levels and that mutants defective in different stress pathways exhibit irregular RNAi inheritance dynamics. Moreover, we discovered that resetting of heritable RNAi is orchestrated by MAPK pathway factors, the transcription factor SKN-1, and the MET-2 methyltransferase. Termination of small RNA inheritance, and the fact that this process depends on stress, could protect from run-on of environment-irrelevant heritable gene regulation.
2021-03-24 | GSE129988 | GEO
Project description:Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individual’s life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring “the phenotype into being”. We used microarrays to determine genes expressed differentially in rats' 4 brain areas - basolateral amygdala (BLA), primary and secondary motor cortex (Crtx), CA1 of the hippocampus (CA1), and CA3 of the hippocampus (CA3) - due to Vinclozolin treatments of their grand-grandmothers and/or to stress in adolescence age. For each of 4 brain areas (BLA, CRTX, CA1, and CA3), RNA samples from 4 treatment groups - stressed control (St-Con), non-stressed control (NSt-Con), stressed vinclozolin (St-Vin), and non-stressed vinclozolin (NSt-Vin) - were compared to each other. Each treatment groups contained 3 biological replica. RNA for each replica was pooled from 4 individual animals forming a certain dyad group.
2012-02-01 | E-GEOD-26737 | biostudies-arrayexpress
Project description:Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To investigate the molecular mechanisms underlying these long-term effects, we exposed adolescent males to stress and measured anxiety behaviors and gene expression in the amygdala-a critical region in the control of emotional states-in their progeny for two generations, offspring and grandoffspring. Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for 2 weeks during adolescence and were used to produce two generations of offspring. Male and female offspring and grandoffspring were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. RNA-seq analysis of the amygdala from male offspring and grandoffspring identified differentially expressed genes (DEGs) in mice derived from fathers exposed to CUS. The DEGSs clustered into numerous pathways, and the "notch signaling" pathway was the most significantly altered in male grandoffspring. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.
| S-EPMC6292780 | biostudies-literature
Project description:Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individual’s life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring “the phenotype into being”. We used microarrays to determine genes expressed differentially in rats' 4 brain areas - basolateral amygdala (BLA), primary and secondary motor cortex (Crtx), CA1 of the hippocampus (CA1), and CA3 of the hippocampus (CA3) - due to Vinclozolin treatments of their grand-grandmothers and/or to stress in adolescence age.
2012-02-01 | GSE26737 | GEO
Project description:The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Numerous toxicant exposures during critical developmental windows can have generational impacts through this non-genetic inheritance mechanism. Pathologies such as delayed pubertal onset, kidney disease and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females from the exposure lineage in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) were also identified in chemotherapy and control lineages sperm in the F1 and F2 generations. The transgenerational alterations in sperm epigenetics provides a molecular mechanism for the ancestral impacts of chemotherapy. Therefore, chemotherapy exposure can impact pathology and disease susceptibility in subsequent generations.
2022-11-30 | GSE217141 | GEO
Project description:Examination of Generational Impacts of Adolescent Chemotherapy: Ifosfamide and Potential for Epigenetic Transgenerational Inheritance
| PRJNA897002 | ENA
Project description:Some epigenetic modifications are inherited from one generation to the next, providing a potential mechanism for the inheritance of environmentally acquired traits. Transgenerational inheritance of RNA interference phenotypes in C. elegans provides an excellent model to study this phenomenon, and whilst studies have implicated both chromatin modifications and small RNA pathways in heritable silencing their relative contributions remain unclear. Here we demonstrate that the histone methyltransferases SET-25 and SET-32 are required for the establishment of a transgenerational silencing signal, but not for long-term maintenance of this signal between subsequent generations suggesting that transgenerational epigenetic inheritance is a multi-step process, with distinct genetic requirements for establishment and maintenance of heritable silencing. Furthermore, small RNA sequencing reveals that the abundance of secondary siRNA (thought to be the effector molecules of heritable silencing) does not correlate with silencing phenotypes. Together, our results suggest that the current mechanistic models of epigenetic inheritance are incomplete.
2018-10-30 | PXD008754 | Pride
Project description:Transcriptome analysis in transgenerational epigenetic inheritance
| PRJNA922492 | ENA