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Status |
Public on Apr 03, 2024 |
Title |
Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Non-coding RNA profiling by high throughput sequencing
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Summary |
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.
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Overall design |
Refer to individual Series
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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
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Department |
Institute of Experimental Genetics (IEG)
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Lab |
Environmental Epigenetics
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Street address |
Ingolstädter Landstraße 1
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City |
München |
ZIP/Postal code |
85764 |
Country |
Germany |
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Platforms (3) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (307)
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This SuperSeries is composed of the following SubSeries:
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GSE239807 |
Mitochondrial signals mediate paternal effects on offspring metabolism (RNA-Seq) |
GSE239808 |
Mitochondrial signals mediate paternal effects on offspring metabolism (scRNA-Seq) |
GSE239810 |
Mitochondrial signals mediate paternal effects on offspring metabolism (small RNA-Seq) |
GSE239814 |
Mitochondrial signals mediate paternal effects on offspring metabolism (Smart-Seq) |
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Relations |
BioProject |
PRJNA1001005 |