title: Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction.
abstract: Pregnancy is a state of high metabolic demand. Fasting diverts metabolism to fatty acid oxidation, and the fasted response occurs much more rapidly in pregnant women than in non-pregnant women. The product of the imprinted DLK1 gene (delta-like homolog 1) is an endocrine signaling molecule that reaches a high concentration in the maternal circulation during late pregnancy. By using mouse models with deleted Dlk1, we show that the fetus is the source of maternal circulating DLK1. In the absence of fetally derived DLK1, the maternal fasting response is impaired. Furthermore, we found that maternal circulating DLK1 levels predict embryonic mass in mice and can differentiate healthy small-for-gestational-age (SGA) infants from pathologically small infants in a human cohort. Therefore, measurement of DLK1 concentration in maternal blood may be a valuable method for diagnosing human disorders associated with impaired DLK1 expression and to predict poor intrauterine growth and complications of pregnancy.
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors: Mary A M
authors: MA
authors: Cleaton
authors: Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors: Claire L
authors: CL
authors: Dent
authors: Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors: Mark
authors: M
authors: Howard
authors: Department of Genetics, University of Cambridge, Cambridge, UK.
authors: Jennifer A
authors: JA
authors: Corish
authors: Department of Genetics, University of Cambridge, Cambridge, UK.
authors: Isabelle
authors: I
authors: Gutteridge
authors: Department of Obstetrics and Gynaecology, University of Cambridge and NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK.
authors: Ulla
authors: U
authors: Sovio
authors: Department of Obstetrics and Gynaecology, University of Cambridge and NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK.
authors: Francesca
authors: F
authors: Gaccioli
authors: Department of Genetics, University of Cambridge, Cambridge, UK.
authors: Nozomi
authors: N
authors: Takahashi
authors: Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, USA.
authors: Steven R
authors: SR
authors: Bauer
authors: Department of Obstetrics and Gynaecology, University of Cambridge and NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK.
authors: D Steven
authors: DS
authors: Charnock-Jones
authors: Department of Pediatrics, Section for Neonatology, University of Colorado Anschutz Medical Campus, Denver, Colorado, USA.
authors: Theresa L
authors: TL
authors: Powell
authors: Department of Obstetrics and Gynaecology, University of Cambridge and NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge, UK.
authors: Gordon C S
authors: GC
authors: Smith
authors: Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.|Department of Genetics, University of Cambridge, Cambridge, UK.
authors: Anne C
authors: AC
authors: Ferguson-Smith
authors: Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors: Marika
authors: M
authors: Charalambous
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis*; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins