Title (eng)

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

Author

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

Publishing

Nature Portfolio

Description (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.

Object languages

English

Date

2024

Rights

This work is licensed under a
CC BY 4.0 - Creative Commons Attribution 4.0 International License.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Classification

Energy Metabolism; Epigenetics; Animals; Male; Spermatozoametabolism; Mice; RNA; Mitochondrial Genetics Metabolism; Female; Epigenesis, Genetic;

Member of the Collection(s) (1)