Characterization of early changes in fetoplacental hemodynamics in a diet-induced rabbit model of IUGR

Abstract

Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research.

Neurodevelopmental Effects of Undernutrition and Placental Underperfusion in Fetal Growth Restriction Rabbit Models

“…As in humans, brain maturation begins in the intrauterine period and continues during the postnatal period. Apart from that, the suitability of PU and UN in rabbits to reproduce human features of FGR has been established [8,10,26] . Finally, another strength of this study is the fact that both models followed the same evaluation protocol in terms of functional test and brain connectivity assessment, offering the possibility to compare the two models.…”

“…While generalized reduction in the uteroplacental blood supply by means of uteroplacental embolization and bilateral uterine artery ligature resulted in nonpredictable reductions of placental perfusion [7] , selective ligature of uteroplacental vessels performed in pregnant rabbits has been demonstrated to develop a gradable model of FGR [8] . Regarding UN models, maternal food deprivation has also demonstrated human FGR characteristics in pregnant rabbits [9,10] .…”

Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR

“…These range 159 from 4 to 34% in progeny of globally nutrient-restricted rats [79,87,88,[93][94][95][96], whilst more severe 160 restriction is seen in models of maternal protein restriction, with 7 to 52% reduction in birth weight 161 in progeny [91,92,[97][98][99][100][101]. The reported decrease in birth weight following the levels of maternal 162 nutrient restriction used in neurodevelopmental studies in sheep and rabbits is milder ranging from 163 9.5% to 17.5% [83,89,102,103]. Effects on fetal nutrient supply and metabolism also differ 164 between the various models of IUGR (Table 1).…”

Animal Models of Fetal Medicine and Obstetrics

“…Calorie restriction is often provided via a 50% restriction diet as notably programs insulin resistance and hypertension [23]. This approach has been adopted by López-Tello, demonstrating a diet-induced IUGR rabbit model, where animals were offered 50% of daily global nutrition, allowing investigations of the early changes in fetoplacental hemodynamics [24]. Interestingly, they found that neonates from this group were significantly smaller than those in the control group, which were offered food ad libitum throughout the pregnancy, and that the IUGR-induced animals showed asymmetrical growth and brain sparing.…”