Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.

ObjectivesChronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring.MethodsF0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing.ResultsNewborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets.ConclusionOur results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.

BackgroundDevelopmental programming of the embryo is controlled by genetic information but also dictated by epigenetic information contained in spermatozoa. Lifestyle and environmental factors not only influence health in one individual but can also affect the phenotype of the following generations. This is mediated via epigenetic inheritance i.e., gametic transmission of environmentally-driven epigenetic information to the offspring. Evidence is accumulating that preconceptional exposure to certain lifestyle and environmental factors, such as diet, physical activity, and smoking, affects the phenotype of the next generation through remodeling of the epigenetic blueprint of spermatozoa.Scope of ReviewThis review will summarize current knowledge about the different epigenetic signals in sperm that are responsive to environmental and lifestyle factors and are capable of affecting embryonic development and the phenotype of the offspring later in life.Major conclusionsLike somatic cells, the epigenome of spermatozoa has proven to be dynamically reactive to a wide variety of environmental and lifestyle stressors. The functional consequence on embryogenesis and phenotype of the next generation remains largely unknown. However, strong evidence of environmentally-driven sperm-borne epigenetic factors, which are capable of altering the phenotype of the next generation, is emerging on a large scale.

Both obesity and T2D are associated with an altered epigenetic signature of the immune system in a cell type-specific manner. These changes could contribute to the altered immune functions associated with obesity and insulin resistance.

Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RRBS), we, respectively, investigated sRNA expression and DNA methylation in pure fractions of motile spermatozoa collected from young healthy individuals before, after 6 weeks of endurance training and after 3 months without exercise. Expression of 8 PIWI interacting RNA were changed by exercise training. RRBS analysis revealed 330 differentially methylated regions (DMRs) after training and 303 DMRs after the detraining period, which were, in both conditions, enriched at close vicinity of transcription start sites. Ontology analysis of genes located at proximity of DMRs returned terms related to neurological function at the trained state and, to a much lesser extent, at the detrained state. Our study reveal that short-term endurance training induces marked remodeling of the sperm epigenome, and identify genes related to the development of the central nervous system as potential hot spots for epigenetic variation upon environmental stress.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0446-7) contains supplementary material, which is available to authorized users.

No abstract

Aim:To determine the genomic mechanisms by which adipose tissue responds to acute and chronic exercise.Methods:We profiled the transcriptomic and epigenetic response to acute exercise in human adipose tissue collected before and after endurance training.Results:Although acute exercises were performed at same relative intensities, the magnitude of transcriptomic changes after acute exercise was reduced by endurance training. DNA methylation remodeling induced by acute exercise was more prominent in trained versus untrained state. We found an overlap between gene expression and DNA methylation changes after acute exercise for 32 genes pre-training and six post-training, notably at adipocyte-specific genes.Conclusion:Training status differentially affects the epigenetic and transcriptomic response to acute exercise in human adipose tissue.

Our findings that preadipocytes retain the memory of the donor in culture and can be reprogrammed by extracellular factors support a mechanism by which adipocyte precursors are epigenetically reprogrammed in vivo. Epigenetic reprogramming of preadipocytes represents a mechanism by which metabolic function of visceral adipose tissue may be affected in the long term by past exposure to obesity- or T2D-specific factors.