Altered Growth, Hypoglycemia, Hypoalaninemia, and Ketonemia in the Young Rat: Postnatal Consequences of Intrauterine Growth Retardation

Ogata, Edward S.; Bussey, Mary E.; Labarbera, Andrew R.; Finley, Sandra

doi:10.1203/00006450-198501000-00010

Cited by 86 publications

(59 citation statements)

References 27 publications

(18 reference statements)

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“…This model produces relatively uniform ischemia throughout the uterus and results in a 42% survival rate and IUGR with a significant brain sparing effect in the pups (Camprubi et al., 2009). As in other vascular models performed at day 17 of gestation (Huizinga et al., 2004) and at E18 (Jansson & Lambert, 1999; Ogata, Bussey, LaBarbera, & Finley, 1985), animals born to CMO mothers did not achieve catch up growth. Simmons, however, reported catch up growth in animals obtained from operated mothers at day E19 (Simmons et al., 2001).…”

Section: Discussionmentioning

confidence: 98%

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

et al. 2017

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IntroductionIntrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.MethodsUtero‐placental insufficiency was induced by meso‐ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry.ResultsPlacental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus.ConclusionsThe results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

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Section: Discussionmentioning

confidence: 98%

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

et al. 2017

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“…Like the human, the IUGR rat fetus is characterized by hypoxia, acidosis, hypoglycemia, and hypoinsulinemia (16,17). These values normalize in the perinatal period (18). At d 21 of life, both male and female IUGR rats weigh significantly less than sham-operated control counterparts (7).…”

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Altered Expression and Function of Mitochondrial β-Oxidation Enzymes in Juvenile Intrauterine-Growth-Retarded Rat Skeletal Muscle

et al. 2001

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Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) affects postnatal metabolism. In juvenile rats, IUGR alters skeletal muscle mitochondrial gene expression and reduces mitochondrial NAD ϩ /NADH ratios, both of which affect ␤-oxidation flux. We therefore hypothesized that gene expression and function of mitochondrial ␤-oxidation enzymes would be altered in juvenile IUGR skeletal muscle. To test this hypothesis, mRNA levels of five key mitochondrial enzymes (carnitine palmitoyltransferase I, trifunctional protein of ␤-oxidation, uncoupling protein-3, isocitrate dehydrogenase, and mitochondrial malate dehydrogenase) and intramuscular triglycerides were quantified in 21-d-old (preweaning) IUGR and control rat skeletal muscle. In isolated skeletal muscle mitochondria, enzyme function of the trifunctional protein of ␤-oxidation and isocitrate dehydrogenase were measured because both enzymes compete for mitochondrial NAD ϩ . Carnitine palmitoyltransferase I, the trifunctional protein of ␤-oxidation, and uncoupling protein 3 mRNA levels were significantly increased in IUGR skeletal muscle, whereas mRNA levels of isocitrate dehydrogenase and mitochondrial malate dehydrogenase were unchanged. Similarly, trifunctional protein of ␤-oxidation activity was increased in IUGR skeletal muscle mitochondria, and isocitrate dehydrogenase activity was unchanged. Interestingly, skeletal muscle triglycerides were significantly increased in IUGR skeletal muscle. We conclude that uteroplacental insufficiency alters IUGR skeletal muscle mitochondrial lipid metabolism, and we speculate that the changes observed in this study play a role in the long-term morbidity associated with IUGR. (Pediatr Res 50: 83-90, 2001) Abbreviations CPTI, carnitine palmitoyltransferase I IUGR, intrauterine growth retardation AGA, appropriate for gestational age ICD, isocitrate dehydrogenase MMD, mitochondrial malate dehydrogenase ND-4L, NADH-ubiquinone oxidoreductase subunit 4L HADH, trifunctional protein of ␤-oxidation HADHA, trifunctional protein of ␤-oxidation ␣ subunit UCP3, uncoupling protein 3 UCP3l, uncoupling protein 3-long isoform UCP3s, uncoupling protein 3-short isoform Uteroplacental insufficiency causes IUGR and is causally related to the development of multiple adult morbidities including insulin resistance, hypertension, coronary heart disease, and dyslipidemia (1). Although the effects of these pathophysiologies are most critically felt during adulthood, evidence exists that metabolism may already be altered in IUGR infants.Several investigators have demonstrated that IUGR infants expend more energy and consume more oxygen than AGA infants (2-6); moreover, Bohler et al.

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“…Although both insulin deficiency and resistance contribute to the IUGR diabetic phenotype, asymmetrical IUGR individuals are often characterized by insulin resistance. Uteroplacental insufficiency, a morbidity associated with many common complications of pregnancy induces asymmetrical IUGR (3,4). In the rat, uteroplacental insufficiency results in juvenile IUGR animals whose glucose homeostasis is abnormal only when physiologically challenged on a pharmacological level (5).…”

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IUGR Alters Postnatal Rat Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Fiber Specific Manner

et al. 2003

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Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of insulin resistance in humans and rats. Aberrant skeletal muscle lipid metabolism contributes to the pathogenesis of insulin resistance. Peroxisome proliferator-activated receptor-␥ co-activator-1 (PGC-1) is a transcriptional co-activator that affects gene expression of key lipid metabolizing enzymes such as carnitine palmitoyltransferase I (mCPTI). Because gene expression of lipid metabolizing enzymes is altered in IUGR postnatal skeletal muscle, and we hypothesized that PGC-1 expression would be similarly affected. To prove this hypothesis, bilateral uterine artery ligation and sham surgery were used to produce IUGR and control rats respectively. Western Blotting demonstrated that PGC-1 hind limb skeletal muscle protein levels were increased in perinatal and postnatal IUGR rats. Conventional RT-PCR demonstrated that PGC-1 mRNA levels were similarly increased in perinatal hind limb skeletal muscle and juvenile extensor digitorum longus (EDL), but were decreased in juvenile soleus. Because a gender specific trend was noted in PGC-1 mRNA levels, real time RT-PCR was used for further differentiation. Real time RT-PCR revealed that changes in postnatal skeletal muscle PGC-1 expression were more marked in male IUGR rats versus female IUGR rats. Down stream targets of PGC-1 followed a similar pattern of expression. We conclude that PGC-1 expression is altered in rat IUGR skeletal muscle and speculate that it contributes to the pathogenesis of insulin resistance in the IUGR rat. Barker's Fetal Origins of Adult Disease Hypothesis proposes that fetal adaptation to a deprived intrauterine milieu leads to permanent changes in cellular biology and systemic physiology (1). Intrauterine growth retardation (IUGR) predisposes affected newborns toward the development of insulin resistance and dyslipidemia (2). Although both insulin deficiency and resistance contribute to the IUGR diabetic phenotype, asymmetrical IUGR individuals are often characterized by insulin resistance. Uteroplacental insufficiency, a morbidity associated with many common complications of pregnancy induces asymmetrical IUGR (3, 4). In the rat, uteroplacental insufficiency results in juvenile IUGR animals whose glucose homeostasis is abnormal only when physiologically challenged on a pharmacological level (5). By adulthood, these IUGR rats develop overt diabetes that is characterized by insulin resistance and hypertriglyceridemia (5,19,20).An important component contributing to the pathogenesis of skeletal muscle insulin resistance is altered fatty acid homeostasis (6, 7

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Altered Growth, Hypoglycemia, Hypoalaninemia, and Ketonemia in the Young Rat: Postnatal Consequences of Intrauterine Growth Retardation

Cited by 86 publications

References 27 publications

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Altered Expression and Function of Mitochondrial β-Oxidation Enzymes in Juvenile Intrauterine-Growth-Retarded Rat Skeletal Muscle

IUGR Alters Postnatal Rat Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Fiber Specific Manner

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