Maternal epidermal growth factor deficiency causes fetal hypoglycemia and intrauterine growth retardation in mice: possible involvement of placental glucose transporter GLUT3 expression

Endocrinology. 1999 Sep;140(9):4236-43. doi: 10.1210/endo.140.9.6993.


We investigated the physiological role of epidermal growth factor (EGF) in fetal growth in mice in which midgestational sialoadenectomy induced maternal EGF deficiency. Sialoadenectomy decreased the fetal weight significantly, indicating that maternal EGF deficiency caused intrauterine growth retardation. The weight of the fetal liver in the sialoadenectomized mice was reduced in proportion to the decrease in body weight (82.7+/-10.2 vs. 70.9+/-10.9 mg), whereas the brain weight was not reduced. Sialoadenectomy significantly decreased the glucose concentration in fetal plasma (86.0+/-13.0 vs. 63.0+/-11.8 mg/dl) without affecting the maternal plasma level of glucose. Transplacental transfer of 3H-2-deoxyglucose was significantly decreased by sialoadenectomy (5.17+/-1.25 vs. 2.94+/-1.02%), but transfer of 14C-aminoisobutyric acid was not affected. Northern blot analysis and in situ hybridization of glucose transporter isoform GLUT1 and GLUT3 messenger RNAs (mRNAs) in placenta revealed that sialoadenectomy significantly reduced the expression of GLUT3 mRNA without affecting GLUT1 mRNA levels. Administration of anti-EGF antiserum enhanced the effects of EGF deficiency, which were almost completely corrected by EGF supplementation. These results indicate that EGF plays an important role in fetal growth by regulating the transplacental supply of glucose via GLUT3 expression in the placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoisobutyric Acids / pharmacokinetics
  • Animals
  • Blood Glucose / metabolism
  • Deoxyglucose / pharmacokinetics
  • Epidermal Growth Factor / blood
  • Epidermal Growth Factor / metabolism*
  • Female
  • Fetal Blood / metabolism*
  • Fetal Growth Retardation / etiology*
  • Fetus / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Hypoglycemia / etiology*
  • Mice
  • Mice, Inbred C3H
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Nerve Tissue Proteins*
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy, Animal / blood
  • Pregnancy, Animal / metabolism*
  • Tissue Distribution / physiology


  • Aminoisobutyric Acids
  • Blood Glucose
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Monosaccharide Transport Proteins
  • Nerve Tissue Proteins
  • Slc2a1 protein, mouse
  • Slc2a3 protein, mouse
  • Epidermal Growth Factor
  • Deoxyglucose
  • Glucose