Maternal Nutrient Restriction in Guinea Pigs as an Animal Model for Inducing Fetal Growth Restriction

Abstract

We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs on pregnancy outcomes, maternal/fetal growth parameters, and blood analytes to further characterize the utility of this model for inducing fetal growth restriction (FGR). Thirty guinea pig sows were fed ad libitum (Control) or 70% of the control diet prepregnant switching to 90% at midpregnancy (MNR). Animals were necropsied near term with weights obtained on all sows, fetuses, and placenta. Fetal blood sampling and organ dissection were undertaken in appropriate for gestational age (AGA) fetuses from Control litters and FGR fetuses from MNR litters using > or < 80 g which approximated the 10th percentile for the population weight distribution of the Control fetuses. MNR fetal demise rates (1/43) were extremely low in contrast to that seen with uterine artery ligation/ablation models, albeit with increased preterm delivery in MNR sows (3 of 15). We confirm that MNR fetuses are smaller and have increased placental/fetal weight ratios as often seen in human FGR infants. We provide justification for using a fetal weight threshold for categorizing AGA Control and FGR-MNR cohorts reducing population variance, and show that FGR-MNR fetuses have asymmetrical organ growth, and are polycythemic and hypoglycemic which are also well associated with moderate FGR in humans. These findings further support the utility of moderate MNR in guinea pigs for inducing FGR with many similarities to that in humans with moderate growth restriction whether resulting from maternal undernourishment or placental insufficiency.

Reproductive performance and gestational effort in relation to dietary fatty acids in guinea pigs

“…As this is apparently not the case in guinea pigs, it can be concluded that these animals are able to accumulate additional energy reserves during gestation, which may be enhanced by feeding on dietary PUFAs. A lower litter size and total litter mass in SFA females may have further been related to less pronounced placental tissues [48], which perhaps also caused a decreased energy allocation in establishing and maintaining these tissues. This would also be supported by a general positive link to the total litter mass, as more and heavier fetuses require more space in the uterus and have to be provided with more oxygen and nutrients, resulting in larger and heavier placentas [41].…”

Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs

“…Sows delivered spontaneously at term (∼67 days) and birth weight was recorded. Guinea pig pups from a UAA pregnancy weighing less than 85 grams were defined as LBW, and pups weighing 90 grams or greater at birth were defined as NBW (Elias et al, 2015). Five days prior to weaning the postnatal control diet (CD, TD: 110240; Harlan Laboratories, Madison, WI, USA) was introduced to the pups through the maternal feeding tray.…”

Maternal Undernutrition and Long-Term Effects on Hepatic Function

“…Human and animal studies of food restriction during pregnancy confirm that maternal undernourishment leads to IUGR depending upon the timing (pre-vs postconception) and severity of the insult [28,29,[55][56][57]. Moreover, like models of uterine ligation, fetal liver growth from MNR dams is compromised at birth followed by rapid postnatal catch-up growth [36,55,58].…”

“…Moreover, like models of uterine ligation, fetal liver growth from MNR dams is compromised at birth followed by rapid postnatal catch-up growth [36,55,58]. However, with models of MNR, the impact of a decrease in maternal and placental weight during pregnancy must also be taken into consideration [55,59]. Sheep and rat studies have demonstrated that MNR leads to glucose intolerance and insulin insensitivity, along with greater hepatic lipid and glycogen content in the offspring [58,60].…”

“…Moreover, like models of uterine ligation, fetal liver growth from MNR dams is compromised at birth followed by rapid postnatal catch-up growth [36,55,58]. However, with models of MNR, the impact of a decrease in maternal and placental weight during pregnancy must also be taken into consideration [55,59].…”