The influence of paternal diet on sncRNA-mediated epigenetic inheritance

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.

Repeated sampling facilitates within- and between-subject modeling of the human sperm transcriptome to identify dynamic and stress-responsive sncRNAs

“…There is a growing appreciation for the importance of the paternal preconception environment in the developmental programming of offspring 1 , 15 , 44 , 48 – 51 . Though the mechanisms underlying this developmental plasticity are likely adaptive, in the context of human health, these effects may be expressed as changes in disease risk or resilience.…”

“…Recent studies focusing on the influence of preconception paternal insults implicate epigenetic processes important for germ cell development and maturation 17 – 46 . Advances in high-throughput next-generation sequencing have revealed highly complex populations of RNA in sperm, and in animal studies, small noncoding RNA (sncRNA) populations have emerged as causal agents in the germline transmission of paternal experience 44 , 47 – 51 . Animal studies have provided the strongest evidence that paternal experiences, including various types of stress, drugs, and dietary manipulations, are associated with lasting changes in sperm RNA expression, where changes in specific miRNA and tRNA fragments have often been reported 17 – 25 , 27 , 28 , 31 , 32 , 36 – 38 , 40 , 41 , 52 , 53 .…”

Aging Induces Profound Changes in sncRNA in Rat Sperm and These Changes Are Modified by Perinatal Exposure to Environmental Flame Retardant

“…Although emerging evidence indicates that sncRNA in spermatozoa may serve as an important channel of epigenetic information transfer to the next generation, our knowledge of factors that affect sperm sncRNA profiles is only starting to emerge. For examples, existing research identified that high-fat diets and low-protein diets can alter the expression of miRNA, piRNA, and tRNA-derived RNA in spermatozoa (reviewed in [ 51 ]). Diet-induced changes in the sncRNA profile were associated with phenotypes displaying insulin resistance, altered body weight, and glucose intolerance.…”

Kernel Fusion Method for Detecting Cancer Subtypes via Selecting Relevant Expression Data

“…Zhang et al ( 2017 ) used DNA methylation to find cancer subtypes on breast cancer. Pan et al ( 2018 ) used copy number variants to identify four cancer subtypes on breast cancer. Zhao et al ( 2009 ) used single-stranded DNA (ssDNA) to find cancer subtypes on lung cancer.…”