title: Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans.
abstract: 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.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Donkin
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Soetkin
authors.initials: S
authors.lastname: Versteyhe
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Lars R
authors.initials: LR
authors.lastname: Ingerslev
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Kui
authors.initials: K
authors.lastname: Qian
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Mie
authors.initials: M
authors.lastname: Mechta
authors.affiliation: University Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen 2100, Denmark.
authors.forename: Loa
authors.initials: L
authors.lastname: Nordkap
authors.affiliation: Steno Diabetes Center, Gentofte 2810, Denmark; Center for Diabetes Research, University of Copenhagen, Gentofte Hospital, Hellerup 2900, Denmark.
authors.forename: Brynjulf
authors.initials: B
authors.lastname: Mortensen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Emil Vincent R
authors.initials: EV
authors.lastname: Appel
authors.affiliation: University Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen 2100, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jørgensen
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre 2650, Denmark.
authors.forename: Viggo B
authors.initials: VB
authors.lastname: Kristiansen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby 2800, Denmark; Center for non-coding RNA in Technology and Health, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg 1870, Denmark.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address: barres@sund.ku.dk.
authors.forename: Romain
authors.initials: R
authors.lastname: Barrès
mesh_terms: D000328:Adult; D050110:Bariatric Surgery; D002490:Central Nervous System / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000601:surgery*; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism; D013851:Thinness / Q000235:genetics; D015431:Weight Loss; D055815:Young Adult
chemical_list: D006657:Histones; D058727:RNA, Small Untranslated