Title
Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs
Language
English
Description (en)
Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus 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 (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement 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, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
Keywords (en)
Energy Metabolism; Epigenetics; Animals; Male; Spermatozoametabolism; Mice; RNA; Mitochondrial Genetics Metabolism; Female; Epigenesis, Genetic;
DOI
10.1038/s41586-024-07472-3
Author of the digital object
A.  Tomar  (Helmholtz Zentrum München / German Center for Diabetes Research)
R.  Teperino  (Helmholtz Zentrum München / German Center for Diabetes Research)
A.  Körner  (Leipzig University)
N.  Kotaja  (University of Turku)
M.  Hrabě de Angelis  (Helmholtz Zentrum München / German Center for Diabetes Research)
S.  Marschall  (Helmholtz Zentrum München / German Center for Diabetes Research)
H.  Fuchs  (Helmholtz Zentrum München / German Center for Diabetes Research)
V.  Gailus-Durner  (Helmholtz Zentrum München / German Center for Diabetes Research)
M.  Vogel  (Leipzig University)
W.  Kiess  (Leipzig University)
K.  Landgraf  (Leipzig University)
M.  Scholz  (Leipzig University)
A.  Kühnapfel  (Leipzig University)
H.  Virtanen  (University of Turku)
J.  Toppari  (University of Turku)
J.  Darr  (Helmholtz Zentrum München / German Center for Diabetes Research)
M.  Lassi  (Helmholtz Zentrum München / German Center for Diabetes Research)
Jörg  Burgstaller  (University of Veterinary Medicine Vienna / Boku University)
Mark  Dahlhoff  (University of Veterinary Medicine Vienna)
Auke  Boersma  (University of Veterinary Medicine Vienna)
Thomas  Kolbe  (University of Veterinary Medicine Vienna / BOKU University)
L.  Makharadze  (Helmholtz Zentrum München / German Center for Diabetes Research)
G.  Comas-Armangué  (Helmholtz Zentrum München / German Center for Diabetes Research)
M.  Gomez-Velazquez  (Helmholtz Zentrum München / German Center for Diabetes Research)
R.  Gerlini  (Helmholtz Zentrum München / German Center for Diabetes Research)
Format
application/pdf
Size
11.8 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Nature
Pages or Volume
27
Volume
630
Number
8017
From Page
720
To Page
727
Publisher
Nature Portfolio
Publication Date
2024
Content
Details
Object type
PDFDocument
Format
application/pdf
Created
02.09.2024 08:39:19
This object is in collection
Metadata
Veterinärmedizinische Universität Wien (Vetmeduni) | Veterinärplatz 1 | 1210 Wien - Österreich | T +43 1 25077-0 | Web: vetmeduni.ac.at