IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep.

Insulin-like growth factor-1 (IGF-1) and insulin are important fetal anabolic hormones. Complications of pregnancy, such as placental insufficiency, can lead to fetal growth restriction (FGR) with low-circulating IGF-1 and insulin concentrations and attenuated glucose-stimulated insulin secretion (GSIS), which likely contribute to neonatal glucose dysregulation. We previously demonstrated that a 1-wk infusion of IGF-1 LR3, an IGF-1 analog with low affinity for IGF-binding proteins and high affinity for the IGF-1 receptor, at 6.

Intrauterine fetal growth restriction in sheep leads to sexually dimorphic programming of Preadipocytes' differentiation potential.

Fetal growth restriction (FGR) is a risk factor for obesity in adult life. Importantly, growth-restricted females are more prone to obesity than males. The mechanisms involved in this sexually dimorphic programming are not known.

Corrigendum: Insulin resistance and dyslipidemia in low-birth-weight goat kids.

[This corrects the article DOI: 10.3389/fvets.2024.

Insulin resistance and dyslipidemia in low-birth-weight goat kids.

Low birth weight (LBW) impairs the development and health of livestock by affecting postnatal growth performance and metabolic health in adulthood. Previous studies on indigenous goats in southwest China showed that LBW goat kids had higher mortality and morbidity rates, including hepatic dyslipidemia and liver damage. However, the mechanism of insulin resistance affecting lipid metabolism under LBW conditions remains unclear.

Elevated Norepinephrine Stimulates Adipocyte Hyperplasia in Ovine Fetuses With Placental Insufficiency and IUGR.

Prevailing hypoxemia and hypoglycemia in near-term fetuses with placental insufficiency-induced intrauterine growth restriction (IUGR) chronically increases norepinephrine concentrations, which lower adrenergic sensitivity and lipid mobilization postnatally, indicating a predisposition for adiposity. To determine adrenergic-induced responses, we examined the perirenal adipose tissue transcriptome from IUGR fetuses with or without hypercatecholaminemia. IUGR was induced in sheep with maternal hyperthermia, and hypercatecholaminemia in IUGR was prevented with bilateral adrenal demedullation.

Decreased Pyruvate but Not Fatty Acid Driven Mitochondrial Respiration in Skeletal Muscle of Growth Restricted Fetal Sheep.

Fetuses with intrauterine growth restriction (FGR) have impaired oxidative and energy metabolism, with persistent consequences on their postnatal development. In this study, we test the hypothesis that FGR skeletal muscle has lower mitochondrial respiration rate and alters the transcriptomic profiles associated with energy metabolism in an ovine model. At late gestation, mitochondrial oxygen consumption rates (OCRs) and transcriptome profiles were evaluated in the skeletal muscle collected from FGR and control fetuses.

Blood Transcriptomic Analyses Reveal Functional Pathways Associated with Thermotolerance in Pregnant Ewes Exposed to Environmental Heat Stress.

Environmental heat stress triggers a series of compensatory mechanisms in sheep that are dependent on their genetic regulation of thermotolerance. Our objective was to identify genes and regulatory pathways associated with thermotolerance in ewes exposed to heat stress. We performed next-generation RNA sequencing on blood collected from 16 pregnant ewes, which were grouped as tolerant and non-tolerant to heat stress according to a physiological indicator.

Sexual dimorphic gene expression profile of perirenal adipose tissue in ovine fetuses with growth restriction.

Worldwide, fetal growth restriction (FGR) affects 7%-10% of pregnancies, or roughly 20.5 million infants, each year. FGR increases not only neonatal mortality and morbidity but also the risk of obesity in later life.

In Vivo Real-Time Study of Drug Effects on Carotid Blood Flow in the Ovine Fetus.

The ability of an organism to maintain a constant blood flow to the brain in response to sudden surges in systemic blood pressure (BP) is known as cerebral autoregulation (CAR), which occurs in the carotid artery. In contrast to full-term neonates, preterm neonates are unable to reduce the cerebral blood flow (CBF) in response to increased systemic BP. In preterm neonates, this exposes the fragile cerebral vessels to high perfusion pressures, leading to their rupture and brain damage.

Vascular Stem Cells and the Role of B-Raf Kinase in Survival, Proliferation, and Apoptosis.

Neovascularization is an essential process in organismal development and aging. With aging, from fetal to adult life, there is a significant reduction in neovascularization potential. However, the pathways which play a role in increased neovascularization potential during fetal life are unknown.

Molecular markers for thermo-tolerance are associated with reproductive and physiological traits in Pelibuey ewes raised in a semiarid environment.

Pelibuey sheep exhibit reproductive activity through the year, but warm weather lowers their fertility and demonstrates physiological limitations of environmental heat stress. Single nucleotide polymorphisms (SNPs) associated with heat stress tolerance in sheep have been reported previously. The objective was to validate the association of seven thermo-tolerance SNP markers with reproductive and physiological traits in Pelibuey ewes raised in a semiarid region.

Primary myoblasts from intrauterine growth-restricted fetal sheep exhibit intrinsic dysfunction of proliferation and differentiation that coincides with enrichment of inflammatory cytokine signaling pathways.

Intrauterine growth restriction (IUGR) is linked to lifelong reductions in muscle mass due to intrinsic functional deficits in myoblasts, but the mechanisms underlying these deficits are not known. Our objective was to determine if the deficits were associated with changes in inflammatory and adrenergic regulation of IUGR myoblasts, as was previously observed in IUGR muscle. Primary myoblasts were isolated from IUGR fetal sheep produced by hyperthermia-induced placental insufficiency (PI-IUGR; n = 9) and their controls (n = 9) and from IUGR fetal sheep produced by maternofetal inflammation (MI-IUGR; n = 6) and their controls (n = 7).

Prenatal Oxygen and Glucose Therapy Normalizes Insulin Secretion and Action in Growth-Restricted Fetal Sheep.

Placental insufficiency (PI) lowers fetal oxygen and glucose concentrations, which disrupts glucose-insulin homeostasis and promotes fetal growth restriction (FGR). To date, prenatal treatments for FGR have not attempted to correct the oxygen and glucose supply simultaneously. Therefore, we investigated whether a 5-day correction of oxygen and glucose concentrations in PI-FGR fetuses would normalize insulin secretion and glucose metabolism.

Hepatic Lipid Accumulation and Dysregulation Associate with Enhanced Reactive Oxygen Species and Pro-Inflammatory Cytokine in Low-Birth-Weight Goats.

Occurrence of low birth weight (LBW) is a major concern in livestock production, resulting in poor postnatal growth, lowered efficiency of feed utilization, and impaired metabolic health in adult life. In the southwest region of China, birth weight of indigenous strains of goats varies seasonally with lower weights in summer and winter, but the metabolic regulation of the LBW offspring is still unknown. In this study, by comparing LBW goats to normal birth weight group, we examined hepatic lipid content in association with regulatory mechanisms.

Tissue-specific responses that constrain glucose oxidation and increase lactate production with the severity of hypoxemia in fetal sheep.

Fetal hypoxemia decreases insulin and increases cortisol and norepinephrine concentrations and may restrict growth by decreasing glucose utilization and altering substrate oxidation. Specifically, we hypothesized that hypoxemia would decrease fetal glucose oxidation and increase lactate and pyruvate production. We tested this by measuring whole body glucose oxidation and lactate production, and molecular pathways in liver, muscle, adipose, and pancreas tissues of fetuses exposed to maternal hypoxemia for 9 days (HOX) compared with control fetal sheep (CON) in late gestation.

Genome-wide association study of a thermo-tolerance indicator in pregnant ewes exposed to an artificial heat-stressed environment.

Environmental heat stress negatively influences sheep production in warm semi-arid regions. An animal's ability to tolerate warm weather is difficult to measure naturally due to environmental variability and genetic variation between animals. In this study we developed a thermo-tolerance indicator (TTI) to define heat stress tolerance in pregnant sheep in a controlled environment.

Uteroplacental nutrient flux and evidence for metabolic reprogramming during sustained hypoxemia.

Gestational hypoxemia is often associated with reduced birth weight, yet how hypoxemia controls uteroplacental nutrient metabolism and supply to the fetus is unclear. This study tested the effects of maternal hypoxemia (HOX) between 0.8 and 0.

Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses.

Intrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fetuses with IUGR. These models provide insight into metabolic dysfunction in skeletal muscle and liver.

Pancreatic Islets Exhibit Dysregulated Adaptation of Insulin Secretion after Chronic Epinephrine Exposure.

Chronic adrenergic stimulation is the dominant factor in impairment of the β-cell function. Sustained adrenergic exposure generates dysregulated insulin secretion in fetal sheep. Similar results have been shown in Min6 under the elevated epinephrine condition, but impairments after adrenergic removal are still unknown and a high rate of proliferation in Min6 has been ignored.

Augmented glucose production is not contingent on high catecholamines in fetal sheep with IUGR.

Fetuses with intrauterine growth restriction (IUGR) have high concentrations of catecholamines, which lowers the insulin secretion and glucose uptake. Here, we studied the effect of hypercatecholaminemia on glucose metabolism in sheep fetuses with placental insufficiency-induced IUGR. Norepinephrine concentrations are elevated throughout late gestation in IUGR fetuses but not in IUGR fetuses with a bilateral adrenal demedullation (IAD) at 0.

Discovery and validation of candidate SNP markers associated to heat stress response in pregnant ewes managed inside a climate-controlled chamber.

Sheep production in desert environments during summer is challenging due to heat stress which reduces feed intake, growth, and fertility. Despite warm conditions, some ewes are able to maintain a normal performance suggesting the existence of genetic bases underlying heat tolerance. Our objective was to discover and validate genetic markers associated with thermo-tolerance in pregnant ewes exposed to warm environmental conditions.

Developmental programming: Prenatal testosterone excess disrupts pancreatic islet developmental trajectory in female sheep.

Prenatal testosterone (T)- treated female sheep manifest juvenile insulin resistance, post-pubertal increase in insulin sensitivity and return to insulin resistance during adulthood. Since compensatory hyperinsulinemia is associated with insulin resistance, altered pancreatic islet ontogeny may contribute towards metabolic defects. To test this, pregnant sheep were treated with or without T propionate from days 30-90 of gestation and pancreas collected from female fetuses at gestational day 90 and female offspring at 21 months-of-age.

Chronically elevated norepinephrine concentrations lower glucose uptake in fetal sheep.

Fetal conditions associated with placental insufficiency and intrauterine growth restriction (IUGR) chronically elevate plasma norepinephrine (NE) concentrations. Our objective was to evaluate the effects of chronically elevated NE on insulin-stimulated glucose metabolism in normally grown, non-IUGR fetal sheep, which are independent of other IUGR-related reductions in nutrients and oxygen availability. After surgical placement of catheters, near-term fetuses received either a saline (control) or NE intravenous infusion with controlled euglycemia.