https://phaidra.vetmeduni.ac.at/o:3466
Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs
Tomar, A.
A.
Tomar
Helmholtz Zentrum München / German Center for Diabetes Research
Teperino, R.
R.
Teperino
0000-0001-8815-1409
Helmholtz Zentrum München / German Center for Diabetes Research
Körner, A.
A.
Körner
0000-0001-6001-0356
Leipzig University
Kotaja, N.
N.
Kotaja
University of Turku
Hrabě de Angelis, M.
M.
Hrabě de Angelis
Helmholtz Zentrum München / German Center for Diabetes Research
Marschall, S.
S.
Marschall
0000-0001-5191-7060
Helmholtz Zentrum München / German Center for Diabetes Research
Fuchs, H.
H.
Fuchs
Helmholtz Zentrum München / German Center for Diabetes Research
Gailus-Durner, V.
V.
Gailus-Durner
0000-0002-6076-0111
Helmholtz Zentrum München / German Center for Diabetes Research
Vogel, M.
M.
Vogel
Leipzig University
Kiess, W.
W.
Kiess
Leipzig University
Landgraf, K.
K.
Landgraf
0000-0002-6878-6033
Leipzig University
Scholz, M.
M.
Scholz
0000-0002-4059-1779
Leipzig University
Kühnapfel, A.
A.
Kühnapfel
0000-0003-3668-0784
Leipzig University
Virtanen, H.
H.
Virtanen
University of Turku
Toppari, J.
J.
Toppari
University of Turku
Darr, J.
J.
Darr
Helmholtz Zentrum München / German Center for Diabetes Research
Lassi, M.
M.
Lassi
Helmholtz Zentrum München / German Center for Diabetes Research
Burgstaller, Jörg
Jörg
Burgstaller
University of Veterinary Medicine Vienna / Boku University
Dahlhoff, Mark
Mark
Dahlhoff
0000-0001-9189-7631
University of Veterinary Medicine Vienna
Boersma, Auke
Auke
Boersma
0000-0002-3066-2836
University of Veterinary Medicine Vienna
Kolbe, Thomas
Thomas
Kolbe
0000-0003-2974-8066
University of Veterinary Medicine Vienna / BOKU University
Makharadze, L.
L.
Makharadze
Helmholtz Zentrum München / German Center for Diabetes Research
Comas-Armangué, G.
G.
Comas-Armangué
Helmholtz Zentrum München / German Center for Diabetes Research
Gomez-Velazquez, M.
M.
Gomez-Velazquez
Helmholtz Zentrum München / German Center for Diabetes Research
Gerlini, R.
R.
Gerlini
Helmholtz Zentrum München / German Center for Diabetes Research
Nature Portfolio
text
eng
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.
Energy Metabolism; Epigenetics; Animals; Male; Spermatozoametabolism; Mice; RNA; Mitochondrial Genetics Metabolism; Female; Epigenesis, Genetic;
http://creativecommons.org/licenses/by/4.0/
https://phaidra.vetmeduni.ac.at/api/object/o:3466/download
10.1038/s41586-024-07472-3
https://phaidra.vetmeduni.ac.at/o:605
application/pdf
Nature 630(8017), 720-727 (2024)
Nature
630
8017
720
727
11.83 MB
2024