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The influence of paternal diet on sncRNA-mediated epigenetic inheritance

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Abstract

The risk of developing metabolic diseases is conferred by genetic predisposition from risk genes and by environmental exposures that can manifest in epigenetic changes. The global rise in obesity and type II diabetes has motivated a search for the epigenetic factors underlying these diseases. The possibility of transgenerational inheritance of epigenetic changes raises questions regarding how spermatozoa transmit acquired epigenetic changes that affect the metabolic health of the next generation. The purpose of this review is to describe current key literature concerning small non-coding RNA (sncRNA), specifically (1) the effects of high-fat or low-protein diets on sncRNA presence in spermatozoa; (2) sncRNA transmission from father to offspring; and (3) the functional effects of inherited sncRNA on offspring metabolic phenotype. Current research has identified alterations in the content of sncRNA subtypes, including microRNA (miRNA), Piwi-interacting RNA (piRNA), and transferRNA (tRNA)-derived small non-coding RNA (tsncRNA), in spermatozoa in response to both high-fat diets and low-protein diets. The altered content of spermatozoa sncRNA due to high-fat diets was associated with a changed phenotype in offspring, with offspring displaying insulin resistance, altered body weight, and glucose intolerance. The altered sncRNA content of spermatozoa due to a low-protein diet was associated with altered levels of lipid metabolites in offspring and decreased expression of specific genes starting in two-cell embryos. The current literature suggests that sncRNAs mediate paternal intergenerational epigenetic inheritance and thus has a direct functional importance, as well as possess biomarker potential, for metabolic diseases. Further research is urgently required to identify the specific sncRNAs with the most profound impacts.

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Abbreviations

endo-siRNA:

Endogenous small interfering RNA

HFD:

High-fat diet

LPD:

Low-protein diet

mRNA:

Messenger RNA

miRNA:

microRNA

piRNA:

Piwi-interacting RNA

rRNA:

Ribosomal RNA

rsRNA:

rRNA-derived small RNA

scRNA:

Small cytoplasmic RNA

sdRNA:

SnoRNA-derived small RNA

snRNA:

Small nuclear RNA

sncRNAs:

Small non-coding RNAs

snoRNA:

Small nucleolar RNA

tRNA:

Transfer RNA

tiRNAs:

tRNA halves

tsncRNA:

tRNA-derived small non-coding RNA

tRFs:

tRNA-derived fragments

tsRNA:

Pre-tRNA-derived small RNA

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Acknowledgements

Stine Thorhauge Bak was supported by a Ph.D. fellowship from Health, Aarhus University, Denmark.

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  1. Department of Biomedicine, Aarhus University, Bartholin Building, 8000, Aarhus C, Denmark

    Line Katrine Klastrup, Stine Thorhauge Bak & Anders Lade Nielsen

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  1. Line Katrine Klastrup
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  2. Stine Thorhauge Bak
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Contributions

Study conception and design was performed by Line Katrine Klastrup (LKK) and Anders Lade Nielsen (ALN). Study analysis and interpretation of data were performed by LKK, Stine Thorhauge Bak (STB) and ALN. Drafting of the manuscript was performed by LKK, STB and ALN. All authors approved the final version of the manuscript. ALN is guarantor for the article and accepts full responsibility for the work, the conduct of the study, and controlled the decision to publish.

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Correspondence to Anders Lade Nielsen.

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Klastrup, L.K., Bak, S.T. & Nielsen, A.L. The influence of paternal diet on sncRNA-mediated epigenetic inheritance. Mol Genet Genomics 294, 1–11 (2019). https://doi.org/10.1007/s00438-018-1492-8

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