Ligation of the Uterine Artery and Early Postnatal Food Restriction – Animal Models for Growth Retardation

Abstract

Intrauterine growth restriction (IUGR) is one of the major causes of short stature in child- and adulthood. The cause of IUGR is unknown, however, an impaired uteroplacental function during the second half of human pregnancy might be an important factor, by affecting the programming of somatotropic axis and leading to postnatal growth failure into adulthood. Two rat models with perinatally induced growth retardation were used to examine the long-term effects of perinatal insults on growth. IUGR rats were prepared from pregnant dams, with a bilateral uterine artery ligation at day 17 of their pregnancy. Since the rat is relatively immature at birth, an early postnatal food restriction model was included as another model to broaden the time window of sensitive period of organogenesis. An individual growth curve was calculated of each animal (n = 813). From these individual growth curves the predicted growth curve for each experimental group was calculated by multilevel analysis. The proposed mathematical model allows us to estimate the growth potentials of these rat models with precision and could provide basic information to investigate the relationships among a number of other variables in future studies. Furthermore, we concluded that both pre- and early postnatal malnutrition leads to irreversible slowing down of postnatal growth.

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

“…This model produces relatively uniform ischemia throughout the uterus and results in a 42% survival rate and IUGR with a significant brain sparing effect in the pups (Camprubi et al., 2009). As in other vascular models performed at day 17 of gestation (Huizinga et al., 2004) and at E18 (Jansson & Lambert, 1999; Ogata, Bussey, LaBarbera, & Finley, 1985), animals born to CMO mothers did not achieve catch up growth. Simmons, however, reported catch up growth in animals obtained from operated mothers at day E19 (Simmons et al., 2001).…”

An Experimental Model of Fetal Growth Restriction Based on Selective Ligature of Uteroplacental Vessels in the Pregnant Rabbit

“…Firstly, the model mimics human pregnancy, since it is based on a reduction of placental supply, inducing a combined restriction of oxygen and nutrients. IUGR models based on food restriction do not reproduce these conditions as the role of the placenta is not considered [34] . In line with this reasoning, hyponutrition models do not result in consistent increases in fetal mortality [35][36][37] , which in humans is a key event in the natural history of growth restriction.…”

Impaired Growth Hormone Receptor Signaling during Non-Catch-Up Growth in Rats Born Small for Gestational Age

“…We used bilateral uterine artery ligation in the last week of gestation, followed by natural birth of SGA rats to induce postnatal growth failure. This model mimicking placental insufficiency in humans might be a better suited model than maternal malnutrition to investigate the association between late suboptimal intrauterine growth and postnatal growth failure [14]. Moreover, we investigated the effect of IUGR on hepatic GHR expression based on protein level rather than mRNA level, which might reflect hepatic tissue responsiveness to GH action more appropriately.…”