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

Abstract Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs) 1 , which influences offspring development and adult phenotypes 1–7 . Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood 8 . 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…