Placental insufficiency improves when intrauterine growth-restricted fetal sheep are administered daily ω-3 polyunsaturated fatty acid infusions

Beer, Haley N; Lacey, Taylor A; Gibbs, Rachel L; Most, Micah S; Hicks, Zena M; Grijalva, Pablo C; Petersen, Jessica L; Yates, Dustin T

doi:10.1093/tas/txab166

Cited by 4 publications

(4 citation statements)

References 8 publications

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“…Specifically, acute fetal normoxia improved insulin secretion in the IUGR fetus prior to reductions in circulating norepinephrine ( Macko et al, 2016 ), and daily maternofetal oxygenation of IUGR pregnancies late in gestation improved post-natal skeletal muscle growth and metabolism without recovering Adrβ 2 content ( Cadaret et al, 2019c ). Recent studies in sheep and other animal models for IUGR have indicated major roles for inflammatory programming ( Cadaret et al, 2019a , b ; Beer et al, 2021 ; Lacey et al, 2021 ; Posont et al, 2021 ), glucocorticoid exposure ( Miller et al, 2012 ; Morrison et al, 2012 ), and poor amino acid balance ( Wai et al, 2018 ; Stremming et al, 2020 ) in the development of IUGR pathologies. Although manipulation of adrenergic activity was effective in improving some key IUGR pathologies, it is clear that a more comprehensive understanding of the independent and interacting mechanisms that contribute to the IUGR phenotype is necessary to fully recover metabolic health in IUGR-born offspring.…”

Section: Adrenergic Programming Is a Mechanistic Driver Of Iugr Outcomesmentioning

confidence: 99%

The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring

Gibbs¹,

Yates²

2021

Front. Anim. Sci.

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Maternofetal stress induces fetal programming that restricts skeletal muscle growth capacity and metabolic function, resulting in intrauterine growth restriction (IUGR) of the fetus. This thrifty phenotype aids fetal survival but also yields reduced muscle mass and metabolic dysfunction after birth. Consequently, IUGR-born individuals are at greater lifelong risk for metabolic disorders that reduce quality of life. In livestock, IUGR-born animals exhibit poor growth efficiency and body composition, making these animals more costly and less valuable. Specifically, IUGR-associated programming causes a greater propensity for fat deposition and a reduced capacity for muscle accretion. This, combined with metabolic inefficiency, means that these animals produce less lean meat from greater feed input, require more time on feed to reach market weight, and produce carcasses that are of less quality. Despite the health and economic implications of IUGR pathologies in humans and food animals, knowledge regarding their specific underlying mechanisms is lacking. However, recent data indicate that adaptive programing of adrenergic sensitivity in multiple tissues is a contributing factor in a number of IUGR pathologies including reduced muscle mass, peripheral insulin resistance, and impaired glucose metabolism. This review highlights the findings that support the role for adrenergic programming and how it relates to the lifelong consequences of IUGR, as well as how dysfunctional adrenergic signaling pathways might be effective targets for improving outcomes in IUGR-born offspring.

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Section: Adrenergic Programming Is a Mechanistic Driver Of Iugr Outcomesmentioning

confidence: 99%

The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring

Gibbs¹,

Yates²

2021

Front. Anim. Sci.

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“…Diminished maternofetal interface slows the movement of O 2 , glucose, and other molecules that cross the placenta via simple or facilitated diffusion ( Regnault et al, 2003 ). Studies in IUGR sheep indicate a 50%–70% disparity in maternofetal O 2 gradients ( Limesand et al, 2007 ; Beer et al, 2021 ). Nutrients that cross via facilitated diffusion or active transport are also slowed by reduced placental expression of transporters.…”

Section: Characteristics Of Iugrmentioning

confidence: 99%

“…Interestingly, concentrations of some amino acids were actually increased in these fetuses, which was presumably a byproduct of reduced protein synthesis ( Armstrong, 1973 ). Even electrolyte homeostasis can be disrupted by placental insufficiency, as fetal blood concentrations of Na + , K + , Ca ++ , and Cl − were increased in IUGR fetal sheep ( Jansson et al, 2006 ; Bacchetta et al, 2009 ; Beer et al, 2021 ; Lacey et al, 2021 ).…”

Section: Characteristics Of Iugrmentioning

confidence: 99%

“…Moreover, dietary ω-3 PUFA supplementation in pregnant rats reduced indicators of placental oxidative stress and increased placental and fetal mass ( Jones et al, 2013 ). Even direct infusion of EPA into the bloodstream of IUGR fetal sheep benefitted placental function, as maternofetal glucose and O 2 gradients were improved ( Beer et al, 2021 ). Importantly, maternal ω-3 PUFA supplements directly benefit the fetus as well as the placenta.…”

Section: Mitigating the Impact Of Iugr With ω-3 Pufamentioning

confidence: 99%

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Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention

White,

Yates

2023

Front. Physiol.

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Intrauterine growth restriction (IUGR) arises when maternal stressors coincide with peak placental development, leading to placental insufficiency. When the expanding nutrient demands of the growing fetus subsequently exceed the capacity of the stunted placenta, fetal hypoxemia and hypoglycemia result. Poor fetal nutrient status stimulates greater release of inflammatory cytokines and catecholamines, which in turn lead to thrifty growth and metabolic programming that benefits fetal survival but is maladaptive after birth. Specifically, some IUGR fetal tissues develop enriched expression of inflammatory cytokine receptors and other signaling cascade components, which increases inflammatory sensitivity even when circulating inflammatory cytokines are no longer elevated after birth. Recent evidence indicates that greater inflammatory tone contributes to deficits in skeletal muscle growth and metabolism that are characteristic of IUGR offspring. These deficits underlie the metabolic dysfunction that markedly increases risk for metabolic diseases in IUGR-born individuals. The same programming mechanisms yield reduced metabolic efficiency, poor body composition, and inferior carcass quality in IUGR-born livestock. The ω-3 polyunsaturated fatty acids (PUFA) are diet-derived nutraceuticals with anti-inflammatory effects that have been used to improve conditions of chronic systemic inflammation, including intrauterine stress. In this review, we highlight the role of sustained systemic inflammation in the development of IUGR pathologies. We then discuss the potential for ω-3 PUFA supplementation to improve inflammation-mediated growth and metabolic deficits in IUGR offspring, along with potential barriers that must be considered when developing a supplementation strategy.

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Going Up Inflame: Reviewing the Underexplored Role of Inflammatory Programming in Stress-Induced Intrauterine Growth Restricted Livestock

Hicks

Yates

2021

Front. Anim. Sci.

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The impact of intrauterine growth restriction (IUGR) on health in humans is well-recognized. It is the second leading cause of perinatal mortality worldwide, and it is associated with deficits in metabolism and muscle growth that increase lifelong risk for hypertension, obesity, hyperlipidemia, and type 2 diabetes. Comparatively, the barrier that IUGR imposes on livestock production is less recognized by the industry. Meat animals born with low birthweight due to IUGR are beset with greater early death loss, inefficient growth, and reduced carcass merit. These animals exhibit poor feed-to-gain ratios, less lean mass, and greater fat deposition, which increase production costs and decrease value. Ultimately, this reduces the amount of meat produced by each animal and threatens the economic sustainability of livestock industries. Intrauterine growth restriction is most commonly the result of fetal programming responses to placental insufficiency, but the exact mechanisms by which this occurs are not well-understood. In uncompromised pregnancies, inflammatory cytokines are produced at modest rates by placental and fetal tissues and play an important role in fetal development. However, unfavorable intrauterine conditions can cause cytokine activity to be excessive during critical windows of fetal development. Our recent evidence indicates that this impacts developmental programming of muscle growth and metabolism and contributes to the IUGR phenotype. In this review, we outline the role of inflammatory cytokine activity in the development of normal and IUGR phenotypes. We also highlight the contributions of sheep and other animal models in identifying mechanisms for IUGR pathologies.

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Placental insufficiency improves when intrauterine growth-restricted fetal sheep are administered daily ω-3 polyunsaturated fatty acid infusions

Cited by 4 publications

References 8 publications

The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring

The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring

Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention

Going Up Inflame: Reviewing the Underexplored Role of Inflammatory Programming in Stress-Induced Intrauterine Growth Restricted Livestock

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