Placental Transfer of Analogs of Glucose and Amino Acids in Experimental Intrauterine Growth Retardation

Abstract

SummaryThe available information on the qualitative and quantitative aspects of maternofetal transfer of these nutrients, as well as data We have the in which One uterine artery is concerning possible alterations in their tissue distribution during ligated to study maternofetal transport and tissue uptake of gluof limited transfer are scanty. cose and amino acids in the intrauterine growth-retarded rat. OnIn order to gain more insight into maternofetal transport and the 18th day of gestation, the artery supplying one uterine horn tissue uptake of glucose and amino acids in IUGR, we have Was ligated. Two days later the rats received I3Hl2-deox~ducose employed the model devised by Wigglesworth (3 I), in which the and 114Cla-aminoisobutyric acid iv. One hour later the growth-artery to one uterine horn is ligated. Our goal in these initial retarded and control fetuses were delivered by Cesarean section studies was primarily to test the assumption that in this model and were obtained' The Uterine blood flow restriction limits the rate of glucose and amino tarded fetuses had an average weight reduction of 27%, signifi-acid transport to the placenta and fetus. To the best of our cantly increased placental to fetal weight ratio and brain to body knowledge, this assumption has not been examined in any animal ratio, and a significantly reduced liver to body ratio. Total radio-system where maternal flow restriction has been induced. In activity derived from tritiated deoxyglucose in whole fetal tissues, exploring placental transport and tissue uptake, further metabom placenta, liver, and brain were significantly decreased in the lism of the in question should ideally be excluded. intrauterine growth-retarded (IUGR) fetuses; this was also true For this reason radioactive analogs of glucose and amino acids per gram of tissue except for liver' Liver to plasma, brrfin .to known to undergo little or no further intracellular alteration were plasma, and whole fetal tissue to plasma 3Hwere slgnlfi-used. The results of some of our initial studies are here. cantly increased in the IUGR group. The radioactivity derived from ['4Cla-aminoisobutyric acid was significantly reduced in whole fetal tissues, placenta, liver, and brain in the IUGR fetuses MATERIALS AND METHODSwhether expressed per whole organ or per gram of tissue. Significant differences in liver to plasma, brain to plasma, and whole ANIMALS AND SURGICAL PROCEDURE tissue to plasma 14C ratios were not observed.The experiment involved six pregnant Sprague-Dawley rats Speculation with accurately timed gestations (within 12 hr). They were caged individually and given free access to Purina laboratory pellets and The large reduction in maternofetal transfer of deoxyglucose tap water until the time of surgery. Experimental intrauterine and a-aminoisobutryric acid when uterine blood flow is reduced growth retardation was induced by slight modification (18) of a raises the possibility that one of the major causes of retarded previously described procedure (31). On the 18th day of ges...

Placental transporter activity and expression in relation to fetal growth

“…Rosso (1977) also fed rats a low-protein diet and found that AIB transfer across the placentas of the resulting growthretarded fetuses was lower than that across the placentas of normally grown fetuses from animals fed a normal diet. Nitzan et al (1979), in the study already described above, found that AIB, as well as glucose, transfer was lower across the placentas of rat fetuses rendered growth retarded by uterine artery ligation than across the placentas of the normally grown fetuses from the sham-operated horns. Similarly, Jansson & Persson (1990) found reduced AIB transfer across the placentas of guinea-pig fetuses rendered growth retarded by uterine artery ligation, although they had found no effect on glucose transfer (see above).…”

“…It should be noted, however, that the SGA and AGA groups in this study were not matched for gestational age, the babies in the former group being born 3-4 weeks earlier on average. As already discussed, AIB transfer across placentas of rat fetuses rendered growth retarded by uterine artery ligation is reduced compared with that across placentas of normally grown fetuses (Nitzan et al 1979). Therefore, we tested whether placental system A activity is different between two such groups of rat fetuses (Glazier, Sibley & Carter, 1996b).…”

“…Some of these babies will have reached their genetic growth potential and will be normal.) Jansson & Persson (1990) found no difference in placental transfer of methyl-glucose (another non-metabolizable glucose analogue) between normal and growth-retarded fetuses in a guinea-pig model of IUGR identical to that used in the rat by Nitzan et al (1979). In sheep, carunclectomy before pregnancy can reduce placental mass and lead to growth retardation.…”

“…Nitzan, Orloff & Schulman (1979) measured transfer of the nonmetabolizable glucose analogue 2-deoxyglucose in rats on the 20th day of pregnancy (term is day 22-23) in which fetuses in one horn had been rendered growth retarded by uterine artery ligation on the 18th day. They found reduced transfer to the growth-retarded fetuses compared with that to normal sized fetuses from the sham-operated horn.…”

Increased Elastic Tissue Defect Formation in the Growth Restricted Brown Norway Rat: A Potential Link Between In Utero Condition and Cardiovascular Disease

“…Because other uterine artery ligation studies have shown reduced organ weights at early time points (21)(22)(23), it is possible that BN rat organ weights are initially decreased in growth restricted pups, but by adulthood, had become similarly proportioned to body mass compared with that of the control groups. Of particular interest was that 16-wk male kidney weight was negatively correlated with IEL defects.…”