Maternal Undernutrition from Early- to Mid-Gestation Leads to Growth Retardation, Cardiac Ventricular Hypertrophy, and Increased Liver Weight in the Fetal Sheep

Abstract

Early gestation is critical for placentomal growth, differentiation, and vascularization, as well as fetal organogenesis. The fetal origins of adult disease hypothesis proposes that alterations in fetal nutrition and endocrine status result in developmental adaptations that permanently change structure, physiology, and metabolism, thereby predisposing individuals to cardiovascular, metabolic, and endocrine disease in adult life. Multiparous ewes were fed to 50% (nutrient restricted) or 100% (control fed) of total digestible nutrients from Days 28 to 78 of gestation. All ewes were weighed weekly and diets adjusted for individual weight loss or gain. Ewes were killed on Day 78 of gestation and gravid uteri recovered. Fetal body and organ weights were determined, and numbers, morphologies, diameters, and weights of all placentomes were obtained. From Day 28 to Day 78, restricted ewes lost 7.4% of body weight, while control ewes gained 7.5%. Maternal and fetal blood glucose concentrations were reduced in restricted versus control pregnancies. Fetuses were markedly smaller in the restricted group than in the control group. Further, restricted fetuses exhibited greater right- and left-ventricular and liver weights per unit fetal weight than control fetuses. No treatment differences were observed in any gross placentomal measurement. However, caruncular vascularity was enhanced in conceptuses from nutrient-restricted ewes but only in twin pregnancies. While these alterations in fetal/placental development may be beneficial to early fetal survival in the face of a nutrient restriction, their effects later in gestation as well as in postnatal life need further investigation.

Litter-size-dependent intrauterine growth restriction in sheep

“…Litter-size-dependent IUGR and nutrition insult The observations that blood flow per foetus in twin pregnancies is less than that in singleton pregnancies (Christenson and Prior, 1978), and that concentrations of glucose in the maternal and foetal circulations are lower in twin than in singleton pregnancies (Vonnahme et al, 2003), support the notion that litter-size-dependent IUGR results from the maternal system's inability fully to support growth of multiple conceptuses. However, three lines of evidence suggest that nutrient supply from the dam to the conceptus may not be the sole rate-limiting factor for foetal growth in pregnancies with multiple foetuses, or at least for twin pregnancies.…”

“…Increases in total foetal body mass in pregnancies with multiple foetuses raise the demand for glucose. Accordingly, plasma concentrations of glucose in the foetus and ewe in the case of twin pregnancies are 20% and 30% less, respectively, than for singleton pregnancies during late gestation (Edwards and McMillen, 2002;Vonnahme et al, 2003). The decline in plasma glucose concentration may be associated with changes in glucosetransporter abundance or activity; however, this has never been investigated in multiple pregnancies.…”

“…Undernutrition to 70% of nutrient requirements (National Research Council (NRC), 1985) throughout gestation also reduced maternal and foetal concentrations of blood glucose in singeltons' pregnancies (Edwards and McMillen, 2002). Similarly, restriction to 50% of nutrient requirements (NRC, 1985) for pregnant ewes carrying singeltons between days 28 and 78 of gestation significantly reduced foetal and placental weights, as well as concentrations of total amino acids and polyamines in both the maternal and foetal plasma (Vonnahme et al, 2003;Kwon et al, 2004).…”

The cardiothoracic ratio in AGA and SGA very low birth weight newborn infants

“…It has also been shown that maternal undernutrition from early-to mid-gestation leads to cardiac hypertrophy in fetal sheep. 8 Further study with GA-matched infants would be required to differentiate differences in cardiac and thoracic growth.…”

The effect of feto-maternal size and childhood growth on left ventricular mass and arterial stiffness in Afro-Caribbean children

“…These include the intrauterine changes in cardiovascular mechanics that redistribute blood flow from body to brain in the presence of fetal growth retardation. [1][2][3][4][5][6] In later life, left ventricular hypertrophy is a strong predictor of stroke, heart failure and coronary artery disease. 7 Growth in infancy and childhood also appear to modulate the risk of hypertension, stroke and coronary artery disease, and thus might relate to left ventricular hypertrophy.…”