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| Status |
Public on Apr 03, 2024 |
| Title |
Mitochondrial signals mediate paternal effects on offspring metabolism (small RNA-Seq) |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Small rna have been studied from cauda spermatozoa and spermatids from mice exposed to HFD and LFD.
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| Contributor(s) |
Teperino R |
| Citation missing |
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| Submission date |
Aug 01, 2023 |
| Last update date |
Apr 04, 2024 |
| Contact name |
Raffaele Teperino |
| E-mail(s) |
raffaele.teperino@helmholtz-muenchen.de
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| Organization name |
Helmholtz Zentrum München
|
| Department |
Institute of Experimental Genetics (IEG)
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| Lab |
Environmental Epigenetics
|
| Street address |
Ingolstädter Landstraße 1
|
| City |
München |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (44)
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| This SubSeries is part of SuperSeries: |
| GSE239815 |
Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs |
|
| Relations |
| BioProject |
PRJNA1001004 |
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