title: Lipid metabolism is associated with developmental epigenetic programming.
abstract: Maternal diet and metabolism impact fetal development. Epigenetic reprogramming facilitates fetal adaptation to these in utero cues. To determine if maternal metabolite levels impact infant DNA methylation globally and at growth and development genes, we followed a clinical birth cohort of 40 mother-infant dyads. Targeted metabolomics and quantitative DNA methylation were analyzed in 1st trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as infant umbilical cord blood plasma (CB). We found very long chain fatty acids, medium chain acylcarnitines, and histidine were: (1) stable in maternal plasma from pregnancy to delivery, (2) significantly correlated between M1, M2, and CB, and (3) in the top 10% of maternal metabolites correlating with infant DNA methylation, suggesting maternal metabolites associated with infant DNA methylation are tightly controlled. Global DNA methylation was highly correlated across M1, M2, and CB. Thus, circulating maternal lipids are associated with developmental epigenetic programming, which in turn may impact lifelong health and disease risk. Further studies are required to determine the causal link between maternal plasma lipids and infant DNA methylation patterns.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Marchlewicz
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.|Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.|Reproductive Sciences Program, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Milewski
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.
authors.forename: Tamara R
authors.initials: TR
authors.lastname: Jones
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Goodrich
authors.affiliation: Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: Tanu
authors.initials: T
authors.lastname: Soni
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Domino
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.
authors.forename: Peter X K
authors.initials: PX
authors.lastname: Song
authors.affiliation: Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.|Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, Michigan, 48109, USA.|Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.|Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: F Burant
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, 48109, USA.|Reproductive Sciences Program, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.|Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.|Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.|Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA.
authors.forename: Vasantha
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D000328:Adult; D001724:Birth Weight; D015992:Body Mass Index; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics*; D055442:Metabolome / Q000235:genetics; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000378:metabolism*