Empowering Translational Research in Fetal Growth Restriction: Sheep and Swine Animal Models

Abstract

Fetal or intrauterine growth restriction (FGR or IUGR) is a concerning health issue not only due to its implications in mortality and morbidity of neonates but also because of its long-term consequences on health and disease risk of the individuals. Its main cause is an insufficient supply of nutrients and oxygen by maternal (malnutrition or hypobaric hypoxia) or placental factors (placental insufficiency) during late gestation, when the requirements of fetus are higher. The availability of reliable animal models would be highly useful for the future development of diagnostic, preventive and therapeutic strategies. Most of the studies using animal models have been performed in rodents, while the use of large animals (sheep and swine) has been scarce. The objective of the current review is to offer an overview on the possibilities of using large animals for conducting translational research on IUGR related to inadequate maternal conditions and/or placental dysfunction.

Polyphenols and IUGR pregnancies: Maternal hydroxytyrosol supplementation improves prenatal and early-postnatal growth and metabolism of the offspring

“…Hence, the findings of the current study may indicate a better adaptation to nutritional challenges of fetuses in the hydroxytyrosol group. These data are reinforced by stronger asymmetrical growth patterns in control piglets than in offspring from treated sows from favoring the development of brain, liver and other viscerae (main characteristics of nutritional IUGR; [46]).…”

Models of Intrauterine growth restriction and fetal programming in rabbits

“…As reviewed by Swanson and David (Swanson & David, ), the benefits of using rodents are undeniable; for example, they are easy to maintain in house, environmentally‐challenge, have a short pregnancy and life span, and are modifiable genetically and display a haemochorial placenta, like humans. The use of sheep also offers advantages; both the ewe and fetal lamb can undergo instrumentation to monitor physiological changes across gestation, the ewe usually carries one or two fetuses and gestational length in the sheep is similar to humans (Anthony, Scheaffer, Wright, & Regnault, ; Gonzalez‐Bulnes, Astiz, Parraguez, Garcia‐Contreras, & Vazquez‐Gomez, ; Morrison, ; Reynolds et al, ). Pig models are beneficial as they are omnivorous and display similar diurnal rhythms, physical activity, and pretnatal and postnatal fat accumulation when compared to humans (Gonzalez‐Bulnes & Chavatte‐Palmer, ; Gonzalez‐Bulnes et al, ; Houpt, Houpt, & Pond, ; Walsh Hentges & Martin, ).…”

“…There were also changes in the heart and kidneys in rabbit kits in response to surgical ligature of uteroplacental vessels. In particular, reduced uteroplacental blood flow decreased fetal heart weight and caused systolic and diastolic dysfunction (Schipke et al, ) in association with an increase in myocardial wall thickness, left ventricular hypovascularisation and hypertrophy, altered expression of metabolic genes, and disorganized cardiomyocyte ultrastructure (reduced sarcomere length and mitochondrial density; Gonzalez‐Tendero et al, ; Guitart‐Mampel et al, ; Gumus et al, ; Schipke et al, ; Torre et al, ). Utero‐placental insufficiency also reduced kidney weight, decreased renal glomeruli number and lead to glomerular capillary congestion and oxidative stress in developing rabbits kits (Bassan et al, ; Figueroa et al, ).…”

Fetal and neonatal programming of postnatal growth and feed efficiency in swine

“…Additionally, concentrations of ammonia in the plasma are 19% lower in the glutamine-supplemented IUGR piglets than in the control group [120], indicating that glutamine stimulates whole-body protein synthesis and inhibits whole-body AA oxidation. These findings have important implications for the nutritional management of compromised young pigs [125], improvement in the utilization of dietary protein for lean tissue growth [126], and the sustainability of global pork production [127]. While leucine supplementation can enhance intestinal development and growth, as well as whole-body growth in piglets with a normal birth weight [128], this method has a detrimental effect in IUGR piglets for yet unknown reasons [129].…”