Maternal nutrient restriction in guinea pigs as an animal model for studying growth-restricted offspring with postnatal catch-up growth

Abstract

We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs with fetal growth restriction (FGR) on offspring body and organ weights, hypothesizing that FGR-MNR animals will show catch-up growth but with organ-specific differences. Guinea pig sows were fed ad libitum (Control) or 70% of the control diet from 4 weeks preconception, switching to 90% at midpregnancy (MNR). Control newborns >95 g [appropriate for gestational age (AGA); n = 37] and MNR newborns <85 g (FGR; n = 37) were monitored until neonatal (~25 days) or adult (~110 days) necropsy. Birth weights and body/organ weights at necropsy were used to calculate absolute and fractional growth rates (FRs). FGR-MNR birth weights were decreased ~32% compared with the AGA-Controls. FGR-MNR neonatal whole body FRs were increased ~36% compared with Controls indicating catch-up growth, with values negatively correlated to birth weights indicating the degree of FGR leads to greater catch-up growth. However, the increase in organ FRs in the FGR-MNR neonates compared with Controls was variable, being similar for the brain and kidneys indicating comparable catch-up growth to that of the whole body and twofold increased for the liver but negligible for the heart indicating markedly increased and absent catch-up growth, respectively. While FGR-MNR body and organ weights were unchanged from the AGA-Controls by adulthood, whole body growth rates were increased. These findings confirm early catch-up growth in FGR-MNR guinea pigs but with organ-specific differences and enhanced growth rates by adulthood, which are likely to have implications for structural alterations and disease risk in later life.

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

“…; Nevin et al . ), which also occurs in humans. Other perinatal compromises also alter postnatal growth trajectories.…”

Body Adiposity and Endocrine Profile of Female Wistar Rats of Distinct Ages that were Early Weaned

“…Such acceleration of growth is due to the higher body weight gain of NPEW and PEW animals in this period. This phenomenon known as "catchup" is the result of metabolic adaptations that allowed the individual to survive in an adverse nutritional environmental [11,44,45].…”

Maternal Undernutrition and Long-Term Effects on Hepatic Function

“…Since IUGR leads to major decreases in fetal liver development, it seems conceivable that the liver has the most to gain in growth during postnatal life [19,20]. Animal models of IUGR support that the undernourished liver undergoes rapid postnatal catch-up growth leading to further metabolic dysfunction, but there is evidence from human studies as well [34][35][36]. For example, infants born small for gestational age (SGA) undergo hypersomatotropism as early as 4 days as a result of increased circulating insulin growth factor 1 (IGF-1) produced by the liver [37].…”

“…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].…”