The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

Autor: Yasmin Panchbhaya, Sarah J. Marzi, Fredrika Åsenius, T.J. Gorrie-Stone, Elizabeth Williamson, David J. Williams, Leonard C. Schalkwyk, Vardhman K. Rakyan, Ama Brew, Michelle L. Holland
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Cancer Research
Physiology
Single Nucleotide Polymorphisms
QH426-470
Biochemistry
Body Mass Index
Epigenesis
Genetic
chemistry.chemical_compound
EPIGENETIC VARIATION
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Child
Genetics (clinical)
Genetics
Genetics & Heredity
0303 health sciences
OUTCOMES
Gene Ontologies
Methylation
Genomics
ATLAS
Middle Aged
Chromatin
Body Fluids
Nucleic acids
Blood
CpG site
Physiological Parameters
Child
Preschool
DNA methylation
Epigenetics
Cellular Types
Anatomy
DNA modification
Life Sciences & Biomedicine
Chromatin modification
Research Article
Chromosome biology
Adult
DNA Replication
Cell biology
Adolescent
Single-nucleotide polymorphism
Gestational Age
Biology
INHERITANCE
Polymorphism
Single Nucleotide
EPIGENOME
03 medical and health sciences
Young Adult
Humans
Obesity
SPERMATOZOA
Molecular Biology
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
METHYLATION PATTERNS
0604 Genetics
Science & Technology
Biology and life sciences
IDENTIFICATION
Genome
Human
Gene Expression Profiling
Body Weight
DNA replication
Infant
Newborn
Computational Biology
Infant
DNA
DNA Methylation
Genome Analysis
Human genetics
Sperm
Germ Cells
chemistry
Gene Expression Regulation
CpG Islands
Gene expression
030217 neurology & neurosurgery
Developmental Biology
Zdroj: PLoS Genetics, Vol 16, Iss 10, p e1009035 (2020)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10−8; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits.
Author summary Research primarily conducted in mice suggests that obesity in fathers can have effects on the health of their offspring via changes in the fathers’ sperm. It is not confirmed whether this is true for humans. In this study, we examined sperm and blood from lean and obese men to understand whether obesity affects DNA methylation in both tissues. DNA methylation can impact on gene function and therefore may affect offspring health. We found that there was almost no association between obesity and DNA methylation in sperm. We also showed that DNA methylation patterns found in the blood of obese individuals are not present in sperm from obese men. Generally, DNA methylation patterns across the whole genome were completely different and uncorrelated between the two tissues. Lastly, we compared DNA methylation patterns in sperm to those in many other tissues, including for example blood and brain samples, and found that sperm has a unique signature of DNA methylation—one that points to genes involved in regulating overall levels of transcription. We conclude that obesity probably does not affect DNA methylation in sperm and that, although more research is needed, if obesity in fathers does influence the health of their children, this process is unlikely to be mediated by spermatozoal DNA methylation.
Databáze: OpenAIRE
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