scholarly journals Polyphenols and IUGR Pregnancies: Intrauterine Growth Restriction and Hydroxytyrosol Affect the Development and Neurotransmitter Profile of the Hippocampus in a Pig Model

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1505
Author(s):  
Natalia Yeste ◽  
Néstor Gómez ◽  
Marta Vázquez-Gómez ◽  
Consolación García-Contreras ◽  
Martí Pumarola ◽  
...  
Keyword(s):  
Body Weight ◽  
Intrauterine Growth Restriction ◽  
Maternal Nutrition ◽  
Neuronal Morphology ◽  
Growth Restriction ◽  
Poor Growth ◽  
Neuronal Markers ◽  
Intrauterine Growth ◽  
Cornu Ammonis ◽  
Neurochemical Changes

Intrauterine growth restriction (IUGR) refers to poor growth of a fetus during pregnancy due to deficient maternal nutrition or oxygen supply. Supplementation of a mother’s diet with antioxidants, such as hydroxytyrosol (HTX), has been proposed to ameliorate the adverse phenotypes of IUGR. In the present study, sows were treated daily with or without 1.5 mg of HTX per kilogram of feed from day 35 of pregnancy (at 30% of the total gestational period), and fetuses were sampled at day 100 of gestation. Fetuses were classified as normal body weight (NBW) or low body weight (LBW) as a consequence of IUGR, constituting four groups: NBW-Control, NBW-HTX, LBW-Control, and LBW-HTX. The brain was removed, and the hippocampus, amygdala, and prefrontal cortex were rapidly dissected. Neuronal markers were studied by immunohistochemistry, and a decrease in the number of mature neurons in the hippocampal Cornu Ammonis subfield 1 (CA1) and the Dentate Gyrus (DG) regions was observed in LBW fetuses together with a higher number of immature neurons and other alterations in neuronal morphology. Furthermore, IUGR conditions altered the neurotransmitter (NT) profile, since an increase in the serotonin (5-HT) pathway was observed in LBW fetuses. Supplementation with HTX was able to reverse the morphological and neurochemical changes, leading both characteristics to values similar to those of NBW fetuses.

scholarly journals Plasma lipid levels and body weight altered by intrauterine growth restriction and postnatal fructose diet in adult rats

2012 ◽  
Vol 73 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Elina Malo ◽  
Meiju Saukko ◽  
Merja Santaniemi ◽  
Mirella Hietaniemi ◽  
Eveliina Lammentausta ◽  
...  
Keyword(s):  
Body Weight ◽  
Intrauterine Growth Restriction ◽  
Plasma Lipid ◽  
Growth Restriction ◽  
Lipid Levels ◽  
Adult Rats ◽  
Intrauterine Growth

scholarly journals Intrauterine Growth Restriction: Hungry for an Answer

Physiology ◽  
2016 ◽  
Vol 31 (2) ◽  
pp. 131-146 ◽  
Author(s):  
Sherin U. Devaskar ◽  
Alison Chu
Keyword(s):  
Intrauterine Growth Restriction ◽  
Epigenetic Modification ◽  
Growth Restriction ◽  
Cardiometabolic Disease ◽  
Lifestyle Modifications ◽  
Poor Growth ◽  
Public Health Burden ◽  
Metabolic Phenotypes ◽  
Intrauterine Growth ◽  
Significant Public Health

Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects.

scholarly journals LEFT VENTRICULAR REMODELING PROCEEDS FROM YOUNG ADULTHOOD INTO MIDLIFE IN INTRAUTERINE GROWTH RESTRICTION BABOONS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S106-S106
Author(s):  
Geoffrey D Clarke ◽  
Hillary Huber ◽  
Cun Li ◽  
Anderson Kuo ◽  
Peter Nathanielsz
Keyword(s):  
Body Weight ◽  
Intrauterine Growth Restriction ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Left Ventricular ◽  
Growth Restriction ◽  
Breath Holding ◽  
Control Group ◽  
Phase Array ◽  
Intrauterine Growth

Abstract Previous cross-sectional studies have shown young adult baboons (~5-6 y.o.), subjected to intrauterine growth restriction (IUGR) by maternal calorie restriction during pregnancy and lactation, exhibit ventricular remodeling with mildly impaired heart function relative to age/sex-matched controls (CTL). METHODS: In this longitudinal study cardiac MRI was performed on male IUGR baboons (n=7). A 3 Tesla, Siemens TIM Trio MRI system was used with phase-array coils with parallel imaging acquisition and breath-holding during the scan. Studies of IUGR animals occurred at 4.7 + 0.1 yr. intervals; the first scan (scan1) at 5.8 + 1.2 y (human equivalent - HE ~24 years) and the second (scan2) at 10.4 + 1.2 yr (HE~40 y). Scans on the CTL animals (N=4) occurred at 5.3 + 1.4 years and 10 + 1.4 years. RESULTS: Change in body weight over 4.7 years was less in the IUGR group (Δwt=6.3 + 6.1 kg) than in the control group (Δwt =11.5 + 8.2 kg). Left ventricular (LV) ejection fraction (EF) was significantly greater in IUGR animals for scan2 (+10.7%, p=0.03) but not in normal controls (+1.8%, p=0.75). Stroke volume and end-diastolic LV volume were normalized to body surface area (BSA). SV/BSA (17.6 + 4.9, 31.5 + 12.3 mL/sq.m; p=0.016) and EDV/BSA (47.3 + 13.6, 64.5 + 18.8 mL/sq.m; p=0.045) were also significantly increased in IUGR animals but not controls. In IUGR subjects, Δweight was significantly and positively correlated with ΔEF (r=0.86, p=0.01). CONCLUSIONS: In IUGR, but not in CTL baboons, cardiac function adaptations continue into midlife and are related to increases in body weight with aging. We conclude that IUGR programs cardiovascular function and that programmed changes continue into midlife.

scholarly journals Isolated Hypomethylation of IGF2 Associated with Severe Hypoglycemia Responsive to Growth Hormone Treatment

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 749
Author(s):  
Sarah C. Grünert ◽  
Uta Matysiak ◽  
Franka Hodde ◽  
Gunda Ruzaike ◽  
Ekkehart Lausch ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Intrauterine Growth Restriction ◽  
Severe Hypoglycemia ◽  
Hormone Treatment ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Poor Growth ◽  
Feeding Difficulties ◽  
Intrauterine Growth ◽  
Pathogenic Variants

Hypomethylation of H19 and IGF2 can cause Silver–Russell syndrome (SRS), a clinically and genetically heterogeneous condition characterized by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, craniofacial abnormalities, body asymmetry, hypoglycemia and feeding difficulties. Isolated hypomethylation of IGF2 has been reported in single cases of SRS as well. Here, we report on a 19-month-old patient who presented with two episodes of hypoglycemic seizures. No intrauterine growth restriction was observed, the patient did not present with SRS-typical facial features, and postnatal growth in the first months of life was along the lower normal percentiles. Exome sequencing did not reveal any likely pathogenic variants explaining the phenotype; however, hypomethylation studies revealed isolated hypomethylation of IGF2, while the methylation of H19 appeared normal. Hypoglycemia responded well to growth hormone therapy, and the boy showed good catch-up growth. Our case demonstrates that SRS and isolated IGF2 hypomethylation should be considered early in the diagnosis of recurrent hypoglycemia in childhood, especially in combination with small gestational age and poor growth.

Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats

2010 ◽  
Vol 298 (1) ◽  
pp. R141-R146 ◽  
Author(s):  
Yasaman Shahkhalili ◽  
Julie Moulin ◽  
Irene Zbinden ◽  
Olivier Aprikian ◽  
Katherine Macé
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Food Intake ◽  
Glucose Intolerance ◽  
Intrauterine Growth Restriction ◽  
Food Restriction ◽  
Plasma Insulin ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Catch Up

Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P < 0.0001), but catch-up growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring ( P < 0.05), thereby contrasting with the lack of significant differences between DEX and CON. These results suggest that prenatal food restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.

scholarly journals The role of gut-liver axis in the restriction of intrauterine growth in a model of experimental gastroschisis

2013 ◽  
Vol 28 (suppl 1) ◽  
pp. 03-07 ◽  
Author(s):  
Márcia Pereira Bueno ◽  
Frances Lilian Lanhellas Gonçalves ◽  
Dioze Guadagnini ◽  
Ricardo Barini ◽  
Mario José Abdalla Saad ◽  
...  
Keyword(s):  
Body Weight ◽  
Experimental Model ◽  
Western Blotting ◽  
Metabolic Pathway ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Pregnant Rats ◽  
Intrauterine Growth

PURPOSE: To evaluate the intrauterine growth restriction (IUGR) by the expression of IR-β, IRS-1, IRS-2, IGF-IRβ and Ikappaβ in experimental model of gastroschisis. METHODS: Pregnant rats at 18.5 days of gestation were submitted to surgery to create experimental fetal gastroschisis (term = 22 days) were divided in three groups: gastroschisis (G), control (C) and sham (S). Fetuses were evaluated for body weight (BW), intestinal (IW), liver (LW) and their relations IW/BW and LW/BW. IR-β and IGF-IRβ receptors, IRS-1 and IRS-2 substrates and Ikappaβ protein were analyzed by western blotting. RESULTS: BW was lower in G, the IW and IW / BW were greater than C and S (p<0.05) groups. The liver showed no differences between groups. In fetuses with gastroschisis, compared with control fetuses, the expression of IGF-IRβ (p<0.001) and Ikappaβ (p<0.001) increased in the liver and intestine, as well as IR-β (p<0.001) which decreased in both. In contrast to the intestine, IRS-1 (p<0.001) increased in the liver and IRS-2 decreased (p<0.01). CONCLUSION: The axis of the intestine liver has an important role in inflammation, with consequent changes in the metabolic pathway of glucose can contribute to the IUGR in fetuses with gastroschisis.

scholarly journals Intrauterine growth restriction alters term fetal baboon hypothalamic appetitive peptide balance

2013 ◽  
Vol 217 (3) ◽  
pp. 275-282 ◽  
Author(s):  
Cun Li ◽  
Thomas J McDonald ◽  
Guoyao Wu ◽  
Mark J Nijland ◽  
Peter W Nathanielsz
Keyword(s):  
Intrauterine Growth Restriction ◽  
Maternal Nutrition ◽  
Regulatory Peptides ◽  
Growth Restriction ◽  
Postnatal Life ◽  
Developmental Studies ◽  
Intrauterine Growth ◽  
Fetal Plasma ◽  
Nuclear Development ◽  
Arcuate Nuclei

Neurons controlling appetite are located in the hypothalamic arcuate nuclei (ARH). Offspring appetite regulation has been shown to be modified by dysregulation of ARH nuclear development. Most ARH developmental studies have been in altricial rodents whose hypothalamic development is predominantly postnatal. In primates including humans, much development of hypothalamic appetite regulatory centers occurs before birth. We hypothesized that i) appetitive peptides are abundantly expressed by 90 percent gestation (0.9G), ready for postnatal function; ii) by 0.9G, intrauterine growth restriction (IUGR) increases the orexigenic:anorexigenic peptide ratio; iii) IUGR increases fetal glucocorticoid receptor (GR) expression; and iv) IUGR decreases STAT3, which signals inhibition of appetite. We developed a fetal baboon IUGR model resulting from reduced maternal nutrition. Pregnant baboons were fed ad libitum, controls (CTR; n=24), or 70% CTR diet to produce IUGR (n=14). C-section was performed at 0.9G. In CTR (n=7) and IUGR (n=6) fetal brains, ARH appetite regulatory peptides (neuropeptide Y (NPY) and proopiomelanocortin (POMC)) were quantified immunohistochemically. Fetal plasma cortisol was raised in IUGR fetuses. We observed that NPY and POMC were well expressed by 0.9G. IUGR increased NPY, GR, and active phosphorylated GR and decreased POMC and phosphorylated form of STAT3. We conclude that IUGR dysregulates ARH development in ways that will reset the appetitive neuropeptide balance in favor of increased appetite drive in postnatal life. We postulate that changes in peptide abundance are in part due to increased fetal cortisol and ARH GR. These changes may contribute to predisposition to obesity in IUGR offspring.

scholarly journals Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction

2017 ◽  
Vol 313 (2) ◽  
pp. R101-R109 ◽  
Author(s):  
Leticia E. Camacho ◽  
Xiaochuan Chen ◽  
William W. Hay ◽  
Sean W. Limesand
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Intrauterine Growth Restriction ◽  
Glucose Utilization ◽  
Placental Insufficiency ◽  
Growth Restriction ◽  
Second Phase ◽  
Metabolic Complications ◽  
Intrauterine Growth

Intrauterine growth restriction (IUGR) is associated with persistent metabolic complications, but information is limited for IUGR infants. We determined glucose-stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR ( n = 7) were compared with control lambs ( n = 8). GSIS was measured at 8 ± 1 days of age, and at 15 ± 1 days, body weight-specific glucose utilization rates were measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp (HEC). IUGR lambs weighed 23% less ( P < 0.05) than controls at birth. Fasting plasma glucose and insulin concentrations were not different between IUGR and controls for either study. First-phase insulin secretion was enhanced 2.3-fold in IUGR lambs compared with controls. However, second-phase insulin concentrations, glucose-potentiated arginine-stimulated insulin secretion, and β-cell mass were not different, indicating that IUGR β-cells have an intrinsic enhancement in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold) and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose utilization was not due to differences in skeletal muscle insulin receptor and glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during HEC were elevated in IUGR lambs compared with controls, but no differences were found for glycogen content or citrate synthase activity in liver and muscle. Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in young lambs are predicted from fetal studies but may promote conditions that exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants.

scholarly journals 258 Deficits in growth, muscle mass, and body composition following intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 199-199
Author(s):  
Rachel L Gibbs ◽  
Rebecca M Swanson ◽  
Joslyn K Beard ◽  
Ty B Schmidt ◽  
Jessica L Petersen ◽  
...  
Keyword(s):  
Body Composition ◽  
Intrauterine Growth Restriction ◽  
Average Daily Gain ◽  
Muscle Growth ◽  
Bioelectrical Impedance ◽  
Growth Restriction ◽  
Lung Weight ◽  
Poor Growth ◽  
Crown Rump Length ◽  
Intrauterine Growth

Abstract Intrauterine growth restriction (IUGR) reduces neonatal muscle growth and alters body composition in livestock. Our objective was to determine the effect of IUGR on juvenile growth and assess the benefits of treatment with clenbuterol (β2 adrenergic agonist) in IUGR offspring. Heat stress-induced IUGR lambs were born 28% lighter (P &lt; 0.05) than controls. At 60 d of age, unsupplemented IUGR lambs had reduced (P &lt; 0.05) bodyweight (BW), average daily gain, and crown-rump length compared to controls, but clenbuterol-supplemented IUGR lambs did not differ from controls. Crown circumference, body girth, and cannon bone length did not differ among groups. Bioelectrical impedance in live lambs and carcasses estimated that lean mass and mass of multiple muscle groups were reduced (P &lt; 0.05) in unsupplemented IUGR lambs but not clenbuterol-supplemented IUGR lambs compared to controls. Estimated protein, fat, and protein/fat were likewise reduced (P &lt; 0.05) in unsupplemented but not clenbuterol-supplemented IUGR lambs. Loin-eye area in chilled carcasses was 30% smaller (P &lt; 0.05) in unsupplemented IUGR lambs but 19% larger (P &lt; 0.05) in clenbuterol-supplemented IUGR lambs compared to controls. Proximate analysis revealed greater (P &lt; 0.05) fat and reduced (P &lt; 0.05) protein and protein/fat in loin muscles from unsupplemented but not clenbuterol-supplemented IUGR lambs compared to controls. At necropsy, hindlimbs, hearts, and flexor digitorum superficialis muscles tended to be lighter (P ≤ 0.09) and lungs and kidneys were lighter (P &lt; 0.05) in IUGR lambs. Kidney weight was further reduced (P &lt; 0.05) in clenbuterol-supplemented IUGR lambs. Brain/BW tended to be reduced (P ≤ 0.09) and lung/BW and kidney/BW were reduced (P &lt; 0.05) in IUGR lambs, but lung weight and lung/BW were greater (P &lt; 0.05) in clenbuterol-supplemented compared to unsupplemented IUGR lambs. We conclude that poor growth and asymmetric body composition previously observed in IUGR neonates persists in juveniles, but daily treatment with clenbuterol recovered growth and improved body composition in IUGR lambs.

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