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

Abstract

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.

Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction

“…Diminished muscle-specific glucose oxidative capacity mediated by the loss of β2 adrenergic regulation reflects a persistent nutrient-sparing fetal programming mechanism in IUGR-born offspring. Skeletal muscle is the largest consumer of glucose [ 1 , 36 ], and even modest β2 adrenergic stimulation increases glucose oxidation rates in normal muscle and myoblasts [ 37 , 38 ]. However, desensitization of β2 adrenoceptors in IUGR muscle coincides with disruption of the TCA cycle and electron transport chain activity late in gestation [ 26 , 39 , 40 ].…”

Blood Mineral Profile in Newborn Calves With Intrauterine Growth Retardation

“…Embryo and fetal intrauterine growth retardation (IUGR), defined as a mismatch between the size of the developing embryo/fetus and gestational age, is a fairly common pathology among livestock [25,51]. According to recent studies [2,36,46], 34.4-37.6% of pregnant cows have IUGR.…”

“…According to recent studies [2,36,46], 34.4-37.6% of pregnant cows have IUGR. The development of IUGR is caused by genetic factors [25,51], malnutrition [23,46,51], endocrine and immune disorders [4,25,27,36], stress [25,26,48], and intoxication [36,44]. Newborns with IUGR often demonstrate body weight deficiency [20,51], are predisposed to metabolic and infectious diseases [6,25,33,51].…”

“…The development of IUGR is caused by genetic factors [25,51], malnutrition [23,46,51], endocrine and immune disorders [4,25,27,36], stress [25,26,48], and intoxication [36,44]. Newborns with IUGR often demonstrate body weight deficiency [20,51], are predisposed to metabolic and infectious diseases [6,25,33,51]. The economic damage from IUGR consists of the costs associated with the treatment, culling and death of such calves [6,9,37], reduction in their growth intensity and feed utilization efficiency [6,20,21,51].…”

“…Despite considerable interest in the problem of IUGR in cattle [11,22,36,44,45], only sporadic studies have investigated metabolic disorders in newborn calves associated with IUGR [6,13,25,33,51]. It has been shown [6,33,51] that newborns with IUGR are characterized by hypoglycemia, hypoxemia, lactoacidosis, insufficiency of antioxidant system and dyslipidemia.…”