Phenotype of early-onset fetal growth restriction in sheep

Abstract

IntroductionFetal growth restriction (FGR) is a common pregnancy complication, caused by placental insufficiency, with serious adverse consequences for development in utero and postnatal wellbeing. There are no antenatal treatments to improve growth or organ development in FGR, and animal models are essential to mimic the physiological adaptations in FGR and to assess potential interventions. This study aimed to identify the temporal nature of reduced developmental trajectory in fetuses with FGR, and to examine the effects of common factors that may mediate differential growth such as glucocorticoid treatment. We hypothesised that the trajectory of growth would be adversely impacted by FGR.MethodsFGR was induced via surgical placental insufficiency in fetal sheep (89 days gestation/0.6 gestation; n=135) and compared to age-matched controls over the last third of gestation and into neonatal life (n=153).ResultsBody weight of FGR fetuses/lambs was significantly reduced compared to controls (p<0.0001) from 127 days of gestation (term is 148 days), with increased brain:body weight ratio (p<0.0001) indicative of brain sparing. All biometric measures of body size were reduced in the FGR group with the exception of biparietal (head) diameter. The trajectory of body growth in the last trimester of sheep pregnancy was significantly reduced in the FGR group compared to controls, and stillbirth rate increased with longer gestation.DiscussionThis work provides a well characterised FGR animal model that mimics the known physiological adaptations in human pregnancy and can be used to determine the efficacy of potential interventions.

Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADRβ2 Content, and Improved Myoblast Function and Muscle Growth

“…Disrupting systemic inflammation in IUGR fetuses improved indicators of body composition and muscle growth. Hallmark asymmetry of the IUGR fetus arises from the preferential sparing of vital brain and heart growth at the expense of muscle and adipose accretion [ 72 , 73 ]. These programmed patterns of disproportional tissue growth persist in IUGR-born offspring [ 13 , 72 , 74 ].…”

“…Hallmark asymmetry of the IUGR fetus arises from the preferential sparing of vital brain and heart growth at the expense of muscle and adipose accretion [ 72 , 73 ]. These programmed patterns of disproportional tissue growth persist in IUGR-born offspring [ 13 , 72 , 74 ]. Although reduced fat deposition is resolved postnatally, reduced muscle mass remains a lifelong deficiency [ 24 , 75 , 76 ].…”