title: Mutations in the glucokinase gene of the fetus result in reduced placental weight.
abstract: OBJECTIVE
  In human pregnancy, placental weight is strongly associated with birth weight. It is uncertain whether there is regulation of the placenta by the fetus or vice versa. We aimed to test the hypothesis that placental growth is mediated, either directly or indirectly, by fetal insulin.
  
  
  METHODS
  Birth weight and placental weight were measured in 43 offspring of 21 parents with mutations in the glucokinase (GCK) gene (25 had inherited the mutation and 18 had not), which results in reduced fetal insulin secretion. Birth weight, placental weight, umbilical cord insulin, and maternal glucose and insulin concentrations were measured in 573 nondiabetic, healthy, term pregnancies.
  
  
  RESULTS
  GCK mutation carriers were lighter and also had smaller placentas (610 vs. 720 g, P = 0.042). This difference was also seen in 17 discordant sibling pairs (600 vs. 720 g, P = 0.003). GCK mRNA was not detected in the placenta by RT-PCR. In the normal pregnancies, placental weight was strongly correlated with birth weight (r = 0.61, P < 0.001). Cord insulin concentrations were directly related to placental weight (r = 0.28) and birth weight (r = 0.36) (P < 0.001 for both).
  
  
  CONCLUSIONS
  These results suggest that insulin, directly or indirectly, plays a role in placental growth, especially as a mutation in the GCK gene, which is known to only alter fetal insulin secretion, results in altered placental weight. This finding is consistent with the preferential localization of the insulin receptors in the fetal endothelium of the placenta in the last trimester of pregnancy.
authors.affiliation: Diabetes Research, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK.
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.forename: Gill
authors.initials: G
authors.lastname: Spyer
authors.forename: Annabelle S
authors.initials: AS
authors.lastname: Slingerland
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Knight
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Clark
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hauguel-de Mouzon
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D001724:Birth Weight; D005260:Female; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009154:Mutation; D010920:Placenta / Q000033:anatomy & histology*; D011247:Pregnancy; D014470:Umbilical Cord / Q000378:metabolism
chemical_list: D007328:Insulin; D005941:Glucokinase