title: Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet.
abstract: 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.
authors.affiliation: Perinatal Center, Institute of Neuroscience and Physiology, Göteborg University, Sweden. nina.jansson@fysiologi.gu.se
authors.forename: Nina
authors.initials: N
authors.lastname: Jansson
authors.forename: Jessica
authors.initials: J
authors.lastname: Pettersson
authors.forename: Allah
authors.initials: A
authors.lastname: Haafiz
authors.forename: Anette
authors.initials: A
authors.lastname: Ericsson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Palmberg
authors.forename: Mattias
authors.initials: M
authors.lastname: Tranberg
authors.forename: Vadivel
authors.initials: V
authors.lastname: Ganapathy
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
mesh_terms: D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D018753:Diet, Protein-Restricted; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D010920:Placenta / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems; D000596:Amino Acids; D007328:Insulin; D020738:Leptin; C412568:Slc38a2 protein, rat; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D005947:Glucose