title: Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth.
abstract: Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34(+) haematopoietic stem/progenitor cells showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.
authors.affiliation: Department of Obstetrics &Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building, Room 631, Bronx, New York 10461, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Delahaye
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Price Building, Room 322, Bronx, New York 10461, USA.
authors.forename: N Ari
authors.initials: NA
authors.lastname: Wijetunga
authors.affiliation: Department of Obstetrics &Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building, Room 631, Bronx, New York 10461, USA.
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Heo
authors.affiliation: Department of Obstetrics &Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building, Room 631, Bronx, New York 10461, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Tozour
authors.affiliation: Department of Obstetrics &Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building, Room 631, Bronx, New York 10461, USA.
authors.forename: Yong Mei
authors.initials: YM
authors.lastname: Zhao
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Price Building, Room 322, Bronx, New York 10461, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Greally
authors.affiliation: Department of Obstetrics &Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building, Room 631, Bronx, New York 10461, USA.
authors.forename: Francine H
authors.initials: FH
authors.lastname: Einstein
mesh_terms: D000328:Adult; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D012727:Sex Characteristics; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D005947:Glucose