In utero glucocorticoid exposure reduces fetal skeletal muscle mass in rats independent of effects on maternal nutrition

Am J Physiol Regul Integr Comp Physiol. 2012 May 15;302(10):R1143-52. doi: 10.1152/ajpregu.00466.2011. Epub 2012 Mar 14.

Abstract

Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n = 7/group) were studied: ad libitum food intake (control, CON); ad libitum food intake with 1 mg dexamethasone/l drinking water from embryonic day (ED)13 to ED21 (DEX); pair-fed (PF) to DEX from ED13 to ED21. On ED22, dams were injected with [(3)H]phenylalanine for measurements of fetal leg muscle and diaphragm fractional protein synthesis rates (FSR). Fetal muscles were analyzed for protein and RNA contents, [(3)H]phenylalanine incorporation, and MuRF1 and atrogin-1 (MAFbx) mRNA expression. Fetal liver tyrosine aminotransferase (TAT) expression was quantified to assess fetal exposure to GLCs. DEX treatment reduced maternal food intake by 13% (P < 0.001) and significantly reduced placental mass relative to CON and PF dams. Liver TAT expression was elevated only in DEX fetuses (P < 0.01). DEX muscle protein masses were 56% and 70% than those of CON (P < 0.01) and PF (P < 0.05) fetuses, respectively; PF muscles were 80% of CON (P < 0.01). Muscle FSR decreased by 35% in DEX fetuses (P < 0.001) but were not different between PF and CON. Only atrogin-1 expression was increased in DEX fetus muscles. We conclude that high maternal GLC levels and inadequate maternal food intake impair fetal skeletal muscle growth, most likely through different mechanisms. When combined, the effects of decreased maternal intake and maternal GLC intake on fetal muscle growth are additive.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Dexamethasone / pharmacology
  • Diaphragm / drug effects
  • Diaphragm / embryology
  • Diaphragm / metabolism
  • Eating / drug effects
  • Eating / physiology
  • Female
  • Fetal Development / drug effects*
  • Fetal Development / physiology
  • Glucocorticoids / pharmacology*
  • Maternal Nutritional Physiological Phenomena / physiology*
  • Models, Animal
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / embryology*
  • Muscle, Skeletal / metabolism
  • Organ Size / drug effects
  • Organ Size / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / physiopathology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Weight Gain / drug effects
  • Weight Gain / physiology

Substances

  • Glucocorticoids
  • Muscle Proteins
  • RNA, Messenger
  • Tripartite Motif Proteins
  • Dexamethasone
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases