Intermittent maternofetal oxygenation during late gestation improved birthweight, neonatal growth, body symmetry, and muscle metabolism in intrauterine growth-restricted lambs.

In humans and animals, intrauterine growth restriction (IUGR) results from fetal programming responses to poor intrauterine conditions. Chronic fetal hypoxemia elevates circulating catecholamines, which reduces skeletal muscle ß2 adrenoceptor content and contributes to growth and metabolic pathologies in IUGR-born offspring. Our objective was to determine whether intermittent maternofetal oxygenation during late gestation would improve neonatal growth and glucose metabolism in IUGR-born lambs. Pregnant ewes were housed at 40 °C from the 40th to 95th day of gestational age (dGA) to produce IUGR-born lambs (n = 9). A second group of IUGR-born lambs received prenatal O2 supplementation via maternal O2 insufflation (100% humidified O2, 10 L/min) for 8 h/d from dGA 130 to parturition (IUGR+O2, n = 10). Control lambs (n = 15) were from pair-fed thermoneutral ewes. All lambs were weaned at birth, hand-reared, and fitted with hindlimb catheters at day 25. Glucose-stimulated insulin secretion (GSIS) and hindlimb hyperinsulinemic-euglycemic clamp (HEC) studies were performed at days 28 and 29, respectively. At day 30, lambs were euthanized and ex vivo HEC studies were performed on isolated muscle. Without maternofetal oxygenation, IUGR lambs were 40% lighter (P < 0.05) at birth and maintained slower (P < 0.05) growth rates throughout the neonatal period compared with controls. At 30 d of age, IUGR lambs had lighter (P < 0.05) hindlimbs and flexor digitorum superficialis (FDS) muscles. IUGR+O2 lambs exhibited improved (P < 0.05) birthweight, neonatal growth, hindlimb mass, and FDS mass compared with IUGR lambs. Hindlimb insulin-stimulated glucose utilization and oxidation rates were reduced (P < 0.05) in IUGR but not IUGR+O2 lambs. Ex vivo glucose oxidation rates were less (P < 0.05) in muscle from IUGR but not IUGR+O2 lambs. Surprisingly, ß2 adrenoceptor content and insulin responsiveness were reduced (P < 0.05) in muscle from IUGR and IUGR+O2 lambs compared with controls. In addition, GSIS was reduced (P < 0.05) in IUGR lambs and only modestly improved (P < 0.05) in IUGR+O2. Insufflation of O2 also increased (P < 0.05) acidosis and hypercapnia in dams, perhaps due to the use of 100% O2 rather than a gas mixture with a lesser O2 percentage. Nevertheless, these findings show that intermittent maternofetal oxygenation during late gestation improved postnatal growth and metabolic outcomes in IUGR lambs without improving muscle ß2 adrenoceptor content.

Sustained heat stress elevated corneal and body surface temperatures and altered circulating leukocytes and metabolic indicators in wether lambs supplemented with ractopamine or zilpaterol.

Understanding how ß adrenergic agonists influence the physiology of heat stress could lead to mitigation options. We sought to investigate body surface temperatures in feedlot wethers supplemented with ractopamine or zilpaterol and exposed to heat stress for 18 d. Corneal and skin temperatures were assessed via infrared thermography at 1- and 2-m distances. Rectal temperatures and circulating leukocytes, metabolites, and electrolytes were also measured. Heat stress increased (P < 0.05) rectal temperatures in unsupplemented and zilpaterol-supplemented lambs but not in ractopamine-supplemented lambs. Heat stress also increased (P < 0.05) surface temperatures of the cornea, nose, ear, and back, regardless of supplement. Observations were comparable between thermography performed at 1 and 2 m, and higher emissivity settings generally produced less variation. Heat stress tended to increase (P = 0.08) blood monocytes in unsupplemented but not ractopamine- or zilpaterol-supplemented lambs. Granulocytes were increased (P < 0.05) by heat stress in ractopamine-supplemented lambs but decreased (P < 0.05) in zilpaterol-supplemented lambs. Blood glucose, triglycerides, and cholesterol did not differ among groups, and blood lactate was reduced (P < 0.05) by heat stress in zilpaterol-supplemented lambs only. Blood Na+ was reduced (P < 0.05) and Ca2+ increased (P < 0.05) by heat stress, regardless of supplement. These findings indicate that ß1- and ß2-adrenergic agonists differentially relieve some but not all heat stress-induced changes in stress indicators. Moreover, corneal and skin surface temperatures measured by infrared thermography reasonably identified body temperature changes at a distance of 2 m.

Lipopolysaccharide endotoxin injections elevated salivary TNFα and corneal temperatures and induced dynamic changes in circulating leukocytes, inflammatory cytokines, and metabolic indicators in wether lambs.

Pathogenic infections increase morbidity and reduce performance in livestock, and thus understanding the comprehensive physiological changes associated with infections can benefit production sustainability. In this study, we sought to investigate such physiological responses to an acute immune challenge in lambs. Polypay wethers received single IV injections of 1.5 µg/kg lipopolysaccharide endotoxin (LPS-injected; n = 6) or saline (controls; n = 6). Corneal temperatures (via infrared thermography), rectal temperatures, blood, plasma, and saliva were assessed every 2 hr for 10 hr after injections. Blood was also assessed at 24 hr. LPS-injected lambs exhibited elevated (P < 0.05) corneal and rectal temperatures that peaked at 4 hr but were still slightly greater (P < 0.05) than controls at 10 hr. Circulating total white blood cells, monocytes, and granulocytes were reduced (P < 0.05) in LPS-injected lambs within the first 4 hr but were subsequently greater (P < 0.05) than in controls. Lymphocytes were reduced (P < 0.05) in LPS-injected lambs over the first 8 hr and did not differ from controls thereafter. Red blood cells, hematocrit, and hemoglobin were increased (P < 0.05) in LPS-injected lambs over the first 6 hr, indicating mild dehydration. Blood glucose briefly increased (P < 0.05) in LPS-injected lambs at 2 hr but was less (P < 0.05) than in controls thereafter. Blood lactate was greater (P < 0.05) in LPS-injected lambs between 6 and 10 hr after injections, which together with reduced (P < 0.05) CO2 partial pressure indicated a metabolic shift toward glycolysis. LPS-injected lambs exhibited a transient increase (P < 0.05) in plasma TNFα at 2 and 4 hr only and sustained increases (P < 0.05) in CXCL9 and CXCL10 beginning at 6 and 4 hr, respectively. They also exhibited a mild, paradoxical increase (P < 0.05) in the anti-inflammatory sFRP3. Salivary TNFα was increased (P < 0.05) in LPS-injected lambs at 2 hr only. Regression analyses indicated that rectal temperatures were a generally poor predictor of the other inflammatory components in this study, with the exception of circulating leukocyte populations. Likewise, correlations among the 10 cytokines measured in this study were generally weak, with notable exceptions between CXCL9 and CXCL10 and between IL-21 and IFNγ. These findings demonstrate that physiological changes to even short-lived immune challenges are dynamic in nature and persist beyond the time frame of febrile responses and other common assessments.

Rapid online teaching: movement of animal science courses online during COVID-19. Case study: pedagogical decisions in transitioning animal science courses online.

Traditionally, earning a degree in animal science requires many face-to-face, hands-on courses; however, the COVID-19 pandemic created a situation in which traditional delivery of these courses may not be feasible as they provide a health risk to our students, teaching assistants, and instructors alike. This examination of two pedagogically different courses and how each was transitioned to an online format highlights the types of teaching decisions that are required to effectively teach animal science in an online format. The Farm Animal Production Systems lab was an animal handling and production practices lab, and although the transition to online delivery did not allow for students to participate in traditional hands-on development of skills, various resources were utilized that still achieved the development of animal handling concepts that will prepare students for later courses and work with live animals. In contrast, the Animal Science Laboratory Teaching Methods course remained consistent in format through the transition to online because students were still able to participate in discussion-based activities via Zoom meetings each week due to the small class size, which helped to maintain student engagement. However, the final teaching experience was modified to an alternative assignment. The alternate assignment included self-reflection and course evaluation that will help to improve both the Farm Animal Production Systems laboratory and the Animal Science Teaching Methods course in the future. Although COVID-19 has been a challenge that disrupted traditional courses, it has provided opportunities for a traditionally hands-on discipline, such as animal science, to more effectively engage students via an online platform.

Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished ß-cell function in fetal sheep1,2.

Maternal inflammation causes fetal intrauterine growth restriction (IUGR), but its impact on fetal metabolism is not known. Thus, our objective was to determine the impact of sustained maternal inflammation in late gestation on fetal inflammation, skeletal muscle glucose metabolism, and insulin secretion. Pregnant ewes were injected every third day from the 100th to 112th day of gestation (term = 150 d) with saline (controls) or lipopolysaccharide (LPS) to induce maternal inflammation and IUGR (MI-IUGR). Fetal femoral blood vessels were catheterized on day 118 to assess ß-cell function on day 123, hindlimb glucose metabolic rates on day 124, and daily blood parameters from days 120 to 125. Fetal muscle was isolated on day 125 to assess ex vivo glucose metabolism. Injection of LPS increased (P < 0.05) rectal temperatures, circulating white blood cells, and plasma tumor necrosis factor α (TNFα) concentrations in MI-IUGR ewes. Maternal leukocytes remained elevated (P < 0.05) and TNFα tended to remain elevated (P < 0.10) compared with controls almost 2 wk after the final LPS injection. Total white blood cells, monocytes, granulocytes, and TNFα were also greater (P < 0.05) in MI-IUGR fetuses than controls over this period. MI-IUGR fetuses had reduced (P < 0.05) blood O2 partial pressures and greater (P < 0.05) maternofetal O2 gradients, but blood glucose and maternofetal glucose gradients did not differ from controls. Basal and glucose-stimulated insulin secretion were reduced (P < 0.05) by 32% and 42%, respectively, in MI-IUGR fetuses. In vivo hindlimb glucose oxidation did not differ between groups under resting conditions but was 47% less (P < 0.05) in MI-IUGR fetuses than controls during hyperinsulinemia. Hindlimb glucose utilization did not differ between fetal groups. At day 125, MI-IUGR fetuses were 22% lighter (P < 0.05) than controls and tended to have greater (P < 0.10) brain/BW ratios. Ex vivo skeletal muscle glucose oxidation did not differ between groups in basal media but was less (P < 0.05) for MI-IUGR fetuses in insulin-spiked media. Glucose uptake rates and phosphorylated-to-total Akt ratios were less (P < 0.05) in muscle from MI-IUGR fetuses than controls regardless of media. We conclude that maternal inflammation leads to fetal inflammation, reduced ß-cell function, and impaired skeletal muscle glucose metabolism that persists after maternal inflammation ceases. Moreover, fetal inflammation may represent a target for improving metabolic dysfunction in IUGR fetuses.

Hypertrophic muscle growth and metabolic efficiency were impaired by chronic heat stress, improved by zilpaterol supplementation, and not affected by ractopamine supplementation in feedlot lambs1.

Feedlot performance is reduced by heat stress and improved by ß adrenergic agonists (ßAA). However, the physiological mechanisms underlying these outcomes are not well characterized, and anecdotal reports suggest that ßAA may confound the effects of heat stress on wellbeing. Thus, we sought to determine how heat stress and ßAA affect growth, metabolic efficiency, and health indicators in lambs on a feedlot diet. Wethers (38.6 ± 1.9 kg) were housed under thermoneutral (controls; n = 25) or heat stress (n = 24) conditions for 21 d. In a 2 × 3 factorial, their diets contained no supplement (unsupplemented), ractopamine (ß1AA), or zilpaterol (ß2AA). Blood was collected on days -3, 3, 9, and 21. On day 22, lambs were harvested and ex vivo skeletal muscle glucose oxidation was determined to gauge metabolic efficiency. Feet and organ tissue damage was assessed by veterinary pathologists. Heat stress reduced (P < 0.05) feed intake by 21%, final bodyweight (BW) by 2.6 kg, and flexor digitorum superficialis (FDS) muscle mass by 5%. ß2AA increased (P < 0.05) FDS mass/BW by 9% and average muscle fiber area by 13% compared with unsupplemented lambs. Blood lymphocytes and monocytes were greater (P < 0.05) in heat-stressed lambs, consistent with systemic inflammation. Plasma insulin was 22% greater (P < 0.05) and glucose/insulin was 16% less (P < 0.05) in heat-stressed lambs than controls. Blood plasma urea nitrogen was increased (P < 0.05) by heat stress on day 3 but reduced (P < 0.05) on days 9 and 21. Plasma lipase and lactate dehydrogenase were reduced (P < 0.05) by heat stress. Glucose oxidation was 17% less (P < 0.05) in muscle from heat-stressed lambs compared with controls and 15% greater (P < 0.05) for ß2AA-supplemented compared with unsupplemented lambs. Environment and supplement interacted (P < 0.05) for rectal temperature, which was increased (P < 0.05) by heat stress on all days but more so (P < 0.05) in ß2AA-supplemented lambs on days 4, 9, and 16. Heat stress increased (P < 0.05) the frequency of hoof wall overgrowth, but ßAA did not produce any pathologies. We conclude that reduced performance in heat-stressed lambs was mediated by reduced feed intake, muscle growth, and metabolic efficiency. ß2AA increased muscle growth and improved metabolic efficiency by increasing muscle glucose oxidation, but no such effects were observed with ractopamine. Finally, ßAA supplementation was not detrimental to health indicators in this study, nor did it worsen the effects of heat stress.

ASAS-SSR Triennnial Reproduction Symposium: Looking Back and Moving Forward-How Reproductive Physiology has Evolved: Fetal origins of impaired muscle growth and metabolic dysfunction: Lessons from the heat-stressed pregnant ewe.

Intrauterine growth restriction (IUGR) is the second leading cause of perinatal mortality and predisposes offspring to metabolic disorders at all stages of life. Muscle-centric fetal adaptations reduce growth and yield metabolic parsimony, beneficial for IUGR fetal survival but detrimental to metabolic health after birth. Epidemiological studies have reported that IUGR-born children experience greater prevalence of insulin resistance and obesity, which progresses to diabetes, hypertension, and other metabolic disorders in adulthood that reduce quality of life. Similar adaptive programming in livestock results in decreased birth weights, reduced and inefficient growth, decreased carcass merit, and substantially greater mortality rates prior to maturation. High rates of glucose consumption and metabolic plasticity make skeletal muscle a primary target for nutrient-sparing adaptations in the IUGR fetus, but at the cost of its contribution to proper glucose homeostasis after birth. Identifying the mechanisms underlying IUGR pathophysiology is a fundamental step in developing treatments and interventions to improve outcomes in IUGR-born humans and livestock. In this review, we outline the current knowledge regarding the adaptive restriction of muscle growth and alteration of glucose metabolism that develops in response to progressively exacerbating intrauterine conditions. In addition, we discuss the evidence implicating developmental changes in ß adrenergic and inflammatory systems as key mechanisms for dysregulation of these processes. Lastly, we highlight the utility and importance of sheep models in developing this knowledge.

A potential role for mTORC1/2 in ß2 adrenergic regulation of skeletal muscle glucose oxidation in models of intrauterine growth restriction.

The epidemic of intrauterine growth restriction (IUGR) continues to be a leading cause of perinatal morbidity and mortality throughout the world. This condition has been linked to the development of metabolic health problems such as obesity, hypertension, glucose intolerance, and type 2 diabetes at all ages. Previous studies have demonstrated that IUGR fetal adaptations impair proper glucose homeostasis in part via changes in insulin responsiveness in key tissues including skeletal muscle and liver, and that these deficits persists into adulthood. Many components of insulin signaling pathways associated with glucose metabolic regulation have been evaluated in IUGR tissues for adaptive changes. Among these are mammalian target of rapamycin complexes 1 and 2 (mTORC1/2) and their associated pathways, which function in mitochondrial control and maintenance. However, recent findings demonstrate that ß2 adrenoceptors (ß2AR) appear to activate an insulin-independent pathway or pathways that modify glucose metabolism via mTORC1/2 complexes. These findings represent a novel potential target for interventions that could improve the treatment and prevention of lUGR-induced metabolic disorders. This review will focus on mechanistic components of ß2AR-mTORC1/2 signaling as well as their role in regulating glucose oxidative metabolism within skeletal muscle.