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Tomar, A. ; Gómez Velázquez, M. ; Gerlini, R. ; Comas-Armangue, G. ; Makharadze, L. ; Kolbe, T.* ; Boersma, A.* ; Dahlhoff, M.* ; Burgstaller, J.P.* ; Lassi, M. ; Darr, J. ; Toppari, J.* ; Virtanen, H.* ; Kühnapfel, A.* ; Scholz, M.* ; Landgraf, K.* ; Kiess, W.* ; Vogel, M.* ; Gailus-Durner, V. ; Fuchs, H. ; Marschall, S. ; Hrabě de Angelis, M. ; Kotaja, N.* ; Körner, A. ; Teperino, R.

Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Nature 638, 720-727 (2024)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Induced Paternal Obesity; Spermatogenesis; Embryo; Spermatozoa; Dysfunction; Biology; Cells
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 638, Heft: , Seiten: 720-727 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
Helmholtz Diabetes Center
PSP-Element(e) G-500693-001
G-500600-001
G-506503-001
Förderungen Christian-Hagedorn project - German Diabetes Society
Minerva Association (ARCHES Prize 2016)
Helmholtz Association (Helmholtz ERC Recognition Award)
Fritz-Thyssen Stiftung
Sigrid Juselius Foundation
Academy of Finland
Pediatric Research Foundation
Turku University Hospital
Novo Nordisk Foundation
Jalmari and Rauha Ahokas Foundation
German Research Foundation (DFG) for the Clinical Research Center 'Obesity Mechanisms
German Diabetes Research Center (DZD Next Grant 2019)
DOI 10.1038/s41586-024-07472-3
WOS ID 001262421300012
Scopus ID 85195262583
PubMed ID 38839949
Erfassungsdatum 2024-06-11
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