Fetus-derived DLK1 is Required for Maternal Metabolic Adaptations to Pregnancy and is Associated with Fetal Growth Restriction

Overview

Journal Nat Genet

Specialty Genetics

Date 2016 Nov 8

PMID 27776119

Citations 39

Authors

Mary A M Cleaton

Claire L Dent

Mark Howard

Jennifer A Corish

Isabelle Gutteridge

Ulla Sovio

Francesca Gaccioli

Nozomi Takahashi

Steven R Bauer

D Steven Charnock-Jones

Theresa L Powell

Gordon C S Smith

Anne C Ferguson-Smith

Marika Charalambous

Affiliations

Soon will be listed here.

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.

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