Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet.

• Intrauterine growth restriction (IUGR) represents an important risk factor for perinatal complications and for adult disease. IUGR is associated with a down-regulation of placental amino acid transporters; however, whether these changes are primary events directly contributing to IUGR or a secondary consequence is unknown. We investigated the time course of changes in placental and fetal growth, placental nutrient transport in vivo and the expression of placental nutrient transporters in pregnant rats subjected to protein malnutrition, a model for IUGR. Pregnant rats were given either a low protein (LP) diet (n = 64) or an isocaloric control diet (n = 66) throughout pregnancy. Maternal insulin, leptin and IGF-I levels decreased, whereas maternal amino acid concentrations increased moderately in response to the LP diet. Fetal and placental weights in the LP group were unaltered compared to control diet at gestational day (GD) 15, 18 and 19 but significantly reduced at GD 21. Placental system A transport activity was reduced at GD 19 and 21 in response to a low protein diet. Placental protein expression of SNAT2 was decreased at GD 21. In conclusion, placental amino acid transport is down-regulated prior to the development of IUGR, suggesting that these placental transport changes are a cause, rather than a consequence, of IUGR. Reduced maternal levels of insulin, leptin and IGF-1 may link maternal protein malnutrition to reduced fetal growth by down-regulation of key placental amino acid transporters.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Amino Acid Transport Systems

genetics

metabolism

Amino Acids

genetics

metabolism

Animals

Biological Transport

genetics

physiology

Diet

Protein-Restricted

Down-Regulation

physiology

Female

Fetal Growth Retardation

metabolism

physiopathology

Gene Expression Regulation

physiology

Glucose

metabolism

Insulin

blood

Insulin-Like Growth Factor I

metabolism

Leptin

blood

Placenta

metabolism

physiopathology

Pregnancy

Protein Kinases

genetics

metabolism

Rats

Rats

Sprague-Dawley

Signal Transduction

genetics

physiology

beta-Alanine

analogs & derivatives

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)