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PROVIDER: PRJNA624261 | ENA |
REPOSITORIES: ENA
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Project description:Paternal exposure to a range of environmental and lifestyle factors elicits distinct changes to the sperm sncRNA profile; modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures effect the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the potent reproductive toxicant, acrylamide. Further, we traced the differential accumulation of acrylamide responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the expression of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identified extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa, the implications of which manifest in the form of dysregulated gene expression during early embryonic development. These data provide a causative mechanistic link to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos
2021-10-07 | PXD022865 | Pride
Project description:Epidemiological studies from the last century have drawn strong associations between paternal life experiences and offspring health and disease outcomes. Recent studies have demonstrated sperm small non-coding RNA (sncRNA) populations vary in response to diverse paternal insults. However, for studies in retrospective or prospective human cohorts to identify changes in paternal germ cell epigenetics in association with offspring disease risk, a framework must first be built with insight into the expected biological variation inherent in human populations. In other words, how will we know what to look for if we don’t first know what is stable and what is dynamic, and what is consistent within and between men over time? From sperm samples from a ‘normative’ cohort of healthy human subjects collected repeatedly from each subject over six months, 17 healthy male participants met inclusion criteria and completed donations and psychological evaluations of perceived stress monthly. sncRNAs (including miRNA, piRNA, and tRNA) isolated from mature sperm from these samples were subjected to Illumina small RNA sequencing, aligned to subtype-specific reference transcriptomes, and quantified. The repeated measures design allowed us to define both within- and between-subject variation in the expression of 254 miRNA, 194 tRNA, and 937 piRNA in sperm over time. We developed screening criteria to identify a subset of potential environmentally responsive ‘dynamic’ sperm sncRNA. Implementing complex modeling of the relationships between individual dynamic sncRNA and perceived stress states in these data, we identified 5 miRNA (including let-7f-5p and miR-181a-5p) and 4 tRNA that are responsive to the dynamics of prior stress experience and fit our established mouse model. In the current study, we aligned repeated sampling of human sperm sncRNA expression data with concurrent measures of perceived stress as a novel framework that can now be applied across a range of studies focused on diverse environmental factors able to influence germ cell programming and potentially impact offspring development.
2020-10-08 | GSE159155 | GEO
Project description:Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have highlighted small non-coding RNAs (sncRNAs) as potential regulators of these effects. This study characterised the baseline sncRNA landscape of human sperm and the effect of a 6 week dietary intervention on their expression profile. 5’tRFs, miRNA and piRNAs were the most abundant sncRNA subtypes identified; their expression was associated with age, BMI and sperm quality. Nutritional intervention with vitamin D and omega-3 fatty acids altered expression of 3 tRFs, 15 miRNAs and 112 piRNAs, targeting genes involved in fatty acid metabolism and transposable elements in the sperm genome.
2021-10-31 | GSE159752 | GEO
Project description:There is a growing body of evidence that inadequate maternal nutrition during gestation can have immediate and life-long effects on offspring. However, little is known about the reproductive effects of maternal gestational nutrition in offspring males. Here, using a sheep model of poor maternal nutrition (restricted- or over-feeding) during gestation, we found that poor maternal gestational nutrition does not affect semen characteristics (i.e. volume, sperm concentration, pH, sperm motility, sperm morphology) and scrotal circumference in offspring. However, by evaluating associations between poor maternal gestational nutrition and altered small non-cording RNAs (sncRNAs) and DNA methylation in offspring sperm, we demonstrated that poor maternal gestational nutrition alters sperm sncRNA composition and expression. Whole genome bisulfite sequencing further identified genomic regions with increased or decreased DNA methylation in sperm in response to poor maternal gestational nutrition. These findings imply that maternal diet-induced epigenetic errors can accumulate in sperm to worsen developmental outcomes of future generations.
2024-04-04 | GSE225985 | GEO
Project description:The discovery of RNAs (e.g. mRNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function in delivering additional paternal information aside from solely providing the DNA1. Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2, 3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat diet (HFD)-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40nt RNA fractions that are induced by HFD. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNA-28S), which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
2018-03-06 | GSE97645 | GEO
Project description:Paternal exposure to environmental stressors elicits distinct changes to the sperm sncRNA profile; modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the reproductive toxicant, acrylamide. Further, we traced the differential accumulation of acrylamide-responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the abundance of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identified extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa, and dysregulated gene expression during early embryonic development following fertilisation by acrylamide-exposed spermatozoa. These data provide mechanistic links to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos.
2021-10-04 | GSE162527 | GEO
Project description:Spermatozoa harbor a complex and environment sensitive pool of small non-coding RNAs (sncRNA)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. We used two distinct paradigms of preconception acute high fat diet to dissect epididymal vs testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs and their fragments (mt-tsRNA) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with BMI and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA-seq of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that alterations of mt-tsRNAs are downstream of mitochondrial dysfunction. Most importantly, single embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilisation and implied them in the control of early embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, for the first time in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
2024-04-03 | GSE239815 | GEO
Project description:There is a growing body of evidence that inadequate maternal nutrition during gestation can have immediate and life-long effects on offspring. However, little is known about the reproductive effects of maternal gestational nutrition in offspring males. Here, using a sheep model of poor maternal nutrition (restricted- or over-feeding) during gestation, we found that poor maternal gestational nutrition does not affect semen characteristics (i.e. volume, sperm concentration, pH, sperm motility, sperm morphology) and scrotal circumference in offspring. However, by evaluating associations between poor maternal gestational nutrition and altered small non-cording RNAs (sncRNAs) and DNA methylation in offspring sperm, we demonstrated that poor maternal gestational nutrition alters sperm sncRNA composition and expression. Whole genome bisulfite sequencing further identified genomic regions with increased or decreased DNA methylation in sperm in response to poor maternal gestational nutrition. These findings imply that maternal diet-induced epigenetic errors can accumulate in sperm to worsen developmental outcomes of future generations.
2024-04-04 | GSE225924 | GEO
Project description:Spermatozoa deliver a complex and environment sensitive pool of small non-coding RNAs (sncRNA) to the oocyte at fertilisation, which influences offspring development and adult phenotypic trajectories. Whether mature spermatozoa in the epididymis can directly sense the environment is still not fully understood. Here, we used two distinct paradigms of preconception acute High Fat Diet challenge to dissect epididymal vs spermatogenic contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNA fragments as sperm-born sensors. In human spermatozoa, we found mt-tsRNAs in linear association with BMI and showed that paternal overweight at conception is sufficient to double offspring obesity risk and compromise metabolic health. Using mouse genetics and metabolic phenotypic data, we show that alterations of mt-tsRNAs are downstream of mitochondrial dysfunction in mice. Most importantly, single embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tsRNAs at fertilisation and implied them in the control of early embryo metabolism. Our study supports the importance of paternal health at conception for offspring metabolism, propose mt-tsRNAs as sperm-born environmental effectors of paternal inheritance and demonstrate, for the first time in a physiological and unperturbed setting, father-to-offspring transfer of sperm mt-tsRNAs at fertilisation.
2024-04-03 | GSE239810 | GEO
Project description:Purpose: Sperm-borne RNA are particularly sensitive to degradation and methodology-induced bias, thus necessitating the use of a consistent, effective RNA extraction protocol for inter-species comparisons. To this end, we established SpermBase, an RNA expression database consisting of small and large RNA expression data obtained using consistent methodologies. Methods: Total RNA was extracted from total sperm and sperm head samples using an RNA extraction protocol that required only slight, species-specific alterations at the lysis stage. Total RNA was subjected to either RNA-Seq (large RNA) or sncRNA-Seq (small RNA). Results: By using a consistent methodology, we were able to perform a cross-species analysis on the conserved features of large and small sperm-borne RNAs. We identified conserved features in both populations of RNAs in the four mammalian species (i.e., mouse, rabbit, rat, and human) surveyed. Conclusions: Our study demonstrates an effective, near-universal approach to the study of sperm-borne RNAs, and identifies conserved characteristics in the large and small RNA populations of mammalian sperm.
2016-05-07 | GSE81216 | GEO