Male obesity effects on sperm and next-generation cord blood DNA methylation

• DOI: 10.1371/journal.pone.0218615
• Publication Date: 2019-06-27T17:35:41Z
• Authors: Ramya Potabattula; Marcus Dittrich; Martin Schorsch; Thomas Hahn; Thomas Haaf; Nady El Hajj
• Keywords: Genomic Imprinting

The prevalence of metabolic disorders, in particular obesity has dramatically increased worldwide. Genetic variants explain only a minor part the epidemic induced by physical inactivity and over-nutrition. Epidemiological studies humans animal models indicate that epigenetic changes associated with adverse parental and/or intrauterine factors may contribute to missing heritability disorders. Possible paternal effects are likely transmitted sperm next-generation. To investigate this hypothesis, we have systematically analyzed male body mass index (BMI) on epigenome its association next-generation fetal cord blood (FCB) DNA methylation. Methylation levels maternally imprinted (PEG1, PEG4, PEG5, PEG10), paternally (H19-IG DMR, IGF2-DMR0, MEG3-IG DMR) regions, obesity-related non-imprinted HIF3A gene were quantified bisulphite pyrosequencing samples 294 human donors undergoing vitro fertilization or intracytoplasmic injection, 113 FCBs resulting offspring. Multivariable regression analyses revealed MEG3 intergenic differentially methylated region (IG showed positive correlation between methylation donor's BMI. A gender-specific BMI FCB was observed for HIF3A, IGF2-DMR0. former two genes displayed same directional nominal (as sperm) Hypomethylation IGF2-DMR0 from female offsprings. Our results suggest is nominally modification methylome humans, which affect Nevertheless, it important note none p-values survived multiple testing adjustments. Future work should test effect aberrations offspring as shown control expression imprint establishment across studied genes.