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.

Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways

“…Maternal protein restriction was reported to decrease maternal serum leptin concentration in rats (FernandezTwinn et al 2003;Jansson et al 2006). However, it was not possible to clarify which of the major sources of leptin in the pregnant mother, adipose tissue or placenta, or both, are affected.…”

“…Under the maternal low protein diet, maternal serum leptin concentration was reported to decrease in the pregnant rat (Fernandez-Twinn et al 2003;Jansson et al 2006). Leptin administration to pregnant rats prevented the decrease in placental 11b-HSD2 activity induced by maternal low protein diet (Stocker et al 2004).…”

Nutrition and human health from a sex–gender perspective

“…For example, low dietary intake of carbohydrates in early pregnancy has been reported to increase placental weight, particularly when combined with high protein intake in late pregnancy (Godfrey et al, 1996). In experimental models of severe maternal undernutrition, both protein malnutrition and the restriction of total caloric intake impair placental and fetal growth (Dwyer et al, 1992;Jansson et al, 2006;Roberts et al, 2001). This observation is reminiscent of reports from the Dutch famine winter during World War II, which showed that exposure to severe caloric restriction early in pregnancy and a high caloric intake in the second half of pregnancy results in increased placental growth (Lumey, 1998).…”

Placental nutrient supply and fetal growth

“…Firstly, inhibition of placental system A activity in pregnant rats, achieved by injecting the mother with high concentrations of MeAIB, is associated with suboptimal fetal growth (Cramer et al, 2002). Secondly, in a rat model of FGR in which dams were fed a protein restricted diet, there was a decrease in placental system A activity that preceded in gestation the decrease in fetal growth (Jansson et al, 2006a). Thirdly, in a mouse model of FGR which displays alterations in placental structure and function that are very similar to those found in human FGR , fetal growth restriction, as in the rat model, is preceded by alterations in placental system A activity (Constancia et al, 2002).…”