ESPEYB21 14. The Year in Science and Medicine Epi-/Genetics (3 abstracts)
14.7. Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs
A. Tomar , M. Gomez-Velazquez , R. Gerlini , G. Comas-Armangué , L. Makharadze , T. Kolbe , A. Boersma , M. Dahlhoff , J.P. Burgstaller , M. Lassi , J. Darr , J. Toppari , H. Virtanen , A. Kühnapfel , M. Scholz , K. Landgraf , W. Kiess , M. Vogel , V. Gailus-Durner , H. Fuchs , S. Marschall , M. Hrabě de Angelis , N. Kotaja , A. Körner & R. Teperino
Nature 630, 720–727 (2024). doi: 10.1038/s41586-024-07472-3
Brief Summary:This study in mice and humans shows how paternal overweight at conception affects the metabolism of their offspring. Sperm-borne mt-sncRNAs (mitochondrial encoded or derived small non-coding RNAs) are altered by a 2-week high fat diet (HFD) challenge in mice, likely through specific upregulation of mt-tsRNAs (mitochondrial transfer RNAs) caused by mitochondrial dysfunction. In humans, mt-tsRNAs in spermatozoa correlate with body mass index. Genetically engineered mice breeding experiments demonstrate how paternal HFD alterations are passed on to offspring by sperm-to-oocyte transfer of mt-tRNAs at fertilization, and thereby influence the early-embryo transcriptome permanently.
It is well known that parental overweight increases the offspring obesity risk and that obesity has multiple adverse health implications. Although the risk for the offspring is higher when the mother is obese, paternal overweight also doubles this risk.
This extensive study shows in great detail and by sophisticated experiments the mechanism how an environmental factor (here HFD) can alter sperm by non-Mendelian genetic means that can then be passed on to the fetus through sperm-to-oocyte interaction. It shows that environmental factors influencing the parents around the time of conception can affect fetal development fundamentally and permanently by epigenetic inheritance of mt-tRNAs.
This study brings new evidence that ‘we are not only what we eat’ but that offspring metabolism is also influenced by parental eating habits and metabolic health at fertilization.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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