Involvement of circulating factors in the transmission of paternal experiences through the germline
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ABSTRACT:
PROVIDER: PRJNA645962 | ENA |
REPOSITORIES: ENA
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Project description:Using a mouse model of paternal exposure to traumatic stress, we identify circulating factors involving peroxisome proliferator-activated receptor (PPAR) pathways in the effects of exposure to the germline. Chronic injection of serum from trauma-exposed males into controls recapitulates metabolic phenotypes in the offspring. Pharmacological PPAR activation in vivo reproduces metabolic dysfunctions in the offspring and grand-offspring of injected males, and affects the sperm transcriptome in fathers and sons. In germ-like cells in vitro, both serum and PPAR agonist induce PPAR activation. Together, these results highlight the role of circulating factors as potential communication vectors between the periphery and the germline.
2020-07-14 | GSE154369 | GEO
Project description: Not available
| S-EPMC7705452 | biostudies-literature
Project description:<p>The gut microbiota operates at the interface of host-environment interactions to influence human homeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore elicit physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline - and consequently on the F1 offspring it gives rise to - is unexplored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory ‘gut-germline axis’ in males, which is sensitive to environmental exposures and programs offspring fitness through impacting placental function.</p>
2024-02-12 | MTBLS1629 | MetaboLights
Project description:Background: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood. Results: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance, both at the phenotypic and molecular levels. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in fetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control. Conclusion: This study reveals a novel role for the histone modifying complex, PRC2, in epigenetic inheritance, with important implications for understanding disease inheritance.
2018-02-15 | GSE110529 | GEO
Project description:Two independent ES cell lines (D4 and C2) were assessed for chimerism and germline transmission. Although these lines were able to produce chimerism at early passage, no germ line transmission was seen. After passaging in a proprietary medium and subcloning by detaching loosely connected cells and culturing in the recommended medium, both lines experienced an increase in potential as evidenced by an enhanced ability to go germ line. Analysis of early passage, and late passage detached and attached cells will allow the determination of genes that may be implicated in the increase of potential seen in these cells. Note: additional replicates may be added at a later date. Keywords: embryonic stem cells, chimerism, germline transmission
2006-01-24 | GSE4087 | GEO
Project description:Mammary gland from F1 CO female offspring exhibited enhanced development when transplanted into OID females [OID(CO-MG)], as shown by higher mammary gland area, epithelial branching and epithelial elongation, compared to CO females that received a CO mammary gland [CO(CO-MG)]. Similarly, mammary tumors from F1 CO female offspring transplanted into OID females [OID(CO.T)] displayed improved growth with higher proliferation index and lower apoptotic rates. We also found that granddaughters (F2) from the OID grand-paternal germline showed accelerated tumor growth compared to COxCO granddaughters (F2). Transmission of breast cancer predisposition to the F2 generation through OID male germline was associated with alterations in sperm tRNA fragments (tRF) in both F0 and F1 males.
2020-11-20 | GSE161831 | GEO
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
Project description:Two independent ES cell lines (D4 and C2) were assessed for chimerism and germline transmission. Although these lines were able to produce chimerism at early passage, no germ line transmission was seen. After passaging in a proprietary medium and subcloning by detaching loosely connected cells and culturing in the recommended medium, both lines experienced an increase in potential as evidenced by an enhanced ability to go germ line. Analysis of early passage, and late passage detached and attached cells will allow the determination of genes that may be implicated in the increase of potential seen in these cells. Note: additional replicates may be added at a later date. Experiment Overall Design: this experiment include 6 samples and 34 replicates
2008-06-12 | E-GEOD-4087 | biostudies-arrayexpress
Project description:Retention of paternal epigenetic memory in the developing teleost germline
| PRJNA506076 | ENA
Project description:Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. However, it is currently unclear how evolutionarily conserved these processes are. Here we characterize the DNA methylomes of zebrafish PGCs at four developmental stages and unravel retention of paternal epigenetic memory, in stark contrast with the findings in mammals. Gene expression profiling of zebrafish PGCs at same developmental stages revealed that the embryonic germline is defined by a small number of markers that display strong developmental stage-specificity and that are uncoupled from DNA methylation-mediated regulation.
2019-07-26 | GSE122722 | GEO