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

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 < 0.05) than controls. At 60 d of age, unsupplemented IUGR lambs had reduced (P < 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 < 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 < 0.05) in unsupplemented but not clenbuterol-supplemented IUGR lambs. Loin-eye area in chilled carcasses was 30% smaller (P < 0.05) in unsupplemented IUGR lambs but 19% larger (P < 0.05) in clenbuterol-supplemented IUGR lambs compared to controls. Proximate analysis revealed greater (P < 0.05) fat and reduced (P < 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 < 0.05) in IUGR lambs. Kidney weight was further reduced (P < 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 < 0.05) in IUGR lambs, but lung weight and lung/BW were greater (P < 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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Obeticholic Acid Protects against Gestational Cholestasis-Induced Fetal Intrauterine Growth Restriction in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7419249 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Wei Chen ◽

Xing-Xing Gao ◽

Li Ma ◽

Zhi-Bing Liu ◽

Li Li ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Glutathione Depletion ◽

Common Disease ◽

Obeticholic Acid ◽

Antioxidant Genes ◽

Crown Rump Length ◽

Intrauterine Growth ◽

Nadph Oxidase 4 ◽

Pregnant Mice

Gestational cholestasis is a common disease and is associated with adverse pregnancy outcomes. However, there are still no effective treatments. We investigated the effects of obeticholic acid (OCA) on fetal intrauterine growth restriction (IUGR) during 17α-ethynylestradiol- (E2-) induced gestational cholestasis in mice. All pregnant mice except controls were subcutaneously injected with E2 (0.625 mg/kg) daily from gestational day (GD) 13 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD12 to GD17. As expected, OCA activated placental, maternal, and fetal hepatic FXR signaling. Additionally, exposure with E2 during late pregnancy induced cholestasis, whereas OCA alleviated E2-induced cholestasis. Gestational cholestasis caused reduction of fetal weight and crown-rump length and elevated the incidence of IUGR. OCA decreased the incidence of IUGR during cholestasis. Interestingly, OCA attenuated reduction of blood sinusoid area in placental labyrinth layer and inhibited downregulation of placental sodium-coupled neutral amino acid transporter- (SNAT-) 2 during cholestasis. Additional experiment found that OCA attenuated glutathione depletion and lipid peroxidation in placenta and fetal liver and placental protein nitration during cholestasis. Moreover, OCA inhibited the upregulation of placental NADPH oxidase-4 and antioxidant genes during cholestasis. OCA activated antioxidant Nrf2 signaling during cholestasis. Overall, we demonstrated that OCA treatment protected against gestational cholestasis-induced placental dysfunction and IUGR through suppressing placental oxidative stress and maintaining bile acid homeostasis.

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Influence of intrauterine growth restriction and gender on body composition and metabolism throughout the life-course

Proceedings of The Nutrition Society ◽

10.1017/s0029665115002232 ◽

2015 ◽

Vol 74 (OCE3) ◽

Cited By ~ 1

Author(s):

J. M. Wallace ◽

J. S. Milne ◽

R. P. Aitken ◽

C. L. Adam

Keyword(s):

Body Composition ◽

Life Course ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Intrauterine Growth ◽

And Gender ◽

The Life Course

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Intrauterine growth restriction and fetal body composition

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.1980 ◽

2005 ◽

Vol 26 (3) ◽

pp. 258-262 ◽

Cited By ~ 55

Author(s):

G. Larciprete ◽

H. Valensise ◽

G. Di Pierro ◽

B. Vasapollo ◽

B. Casalino ◽

...

Keyword(s):

Body Composition ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Intrauterine Growth

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Intrauterine Growth Restriction: Hungry for an Answer

Physiology ◽

10.1152/physiol.00033.2015 ◽

2016 ◽

Vol 31 (2) ◽

pp. 131-146 ◽

Cited By ~ 26

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.

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Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

Cells ◽

10.3390/cells10051007 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1007

Author(s):

Asghar Ali ◽

Eduard Murani ◽

Frieder Hadlich ◽

Xuan Liu ◽

Klaus Wimmers ◽

...

Keyword(s):

Skeletal Muscle ◽

Fetal Growth ◽

Intrauterine Growth Restriction ◽

Muscle Development ◽

Muscle Growth ◽

The Body ◽

Growth Restriction ◽

Economic Losses ◽

Biological Processes ◽

Intrauterine Growth

Intrauterine growth restriction (IUGR) occurs in 15–20% of pig neonates and poses huge economic losses to the pig industry. IUGR piglets have reduced skeletal muscle growth, which may persist after birth. Prenatal muscle growth is regulated by complex molecular pathways that are not well understood. MicroRNAs (miRNAs) have emerged as the main regulators of vital pathways and biological processes in the body. This study was designed to identify miRNA–mRNA networks regulating prenatal skeletal muscle development in pigs. We performed an integrative miRNA–mRNA transcriptomic analysis in longissimus dorsi muscle from IUGR fetuses and appropriate for gestational age (AGA) fetuses at 63 days post conception. Our data showed that 47 miRNAs and 3257 mRNAs were significantly upregulated, and six miRNAs and 477 mRNAs were significantly downregulated in IUGR compared to AGA fetuses. Moreover, 47 upregulated miRNAs were negatively correlated and can potentially target 326 downregulated genes, whereas six downregulated miRNAs were negatively correlated and can potentially target 1291 upregulated genes. These miRNA–mRNA networks showed enrichment in biological processes and pathways critical for fetal growth, development, and metabolism. The miRNA–mRNA networks identified in this study can potentially serve as indicators of prenatal fetal growth and development as well as postnatal carcass quality.

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Analysis of fetal growth restriction in pregnancy in subjects attending in an obstetric clinic of a tertiary care teaching hospital

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20180876 ◽

2018 ◽

Vol 7 (3) ◽

pp. 973

Author(s):

Ashish Seal ◽

Arup Dasgupta ◽

Mousumi Sengupta ◽

Rinini Dastider ◽

Sukanta Sen

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Intrauterine Growth Restriction ◽

Tertiary Care ◽

Growth Restriction ◽

Growth Potential ◽

Crown Rump Length ◽

Mortality And Morbidity ◽

Intrauterine Growth ◽

In Pregnancy

Background: Intrauterine growth restriction (IUGR) is defined as fetal growth less than the normal growth potential of a specific infant because of genetic or environmental factors. Fetal growth restriction or intrauterine growth restriction is one of the leading causes of perinatal mortality and morbidity in newborns. Fetal growth restriction is a complex multifactorial condition resulting from several fetal and maternal disorders. Objective of present study was to find out incidence of IUGR and assessment and evaluation of different important changes in IUGR.Methods: Women who attended the Obstetric OPD in their 1st trimester of pregnancy and those who were thought would be able to visit the antenatal clinic for their fortnightly check-up regularly were screened for intrauterine foetal growth retardation. Women with irregular and uncertain menstrual history and where the 1st trimester USG foetal crown rump length did not corroborate with the menstrual gestational age were excluded from this study.Results: Incidence of IUGR was 18.2% and 84% were found to be asymmetrical. IUGR was found to be double among primigravids and women above 30 years. It had been observed that IUGR was associated with certain conditions like short stature (52%), pregnancy induced hypertension (24%) and anaemia (12%).Conclusions: Thus, early USG screening along with robust screening for maternal BMI, nutritional status, and anaemia can assist the obstetric team in providing early diagnosis, prompt intervention, and better outcome in pregnancy with fetal growth restriction.

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P10.19: Intrauterine growth restriction and fetal body composition

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.2483 ◽

2005 ◽

Vol 26 (4) ◽

pp. 443-444

Author(s):

G. Di Pierro ◽

G. Larciprete ◽

B. Vasapollo ◽

G. Novelli ◽

B. Casalino ◽

...

Keyword(s):

Body Composition ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Intrauterine Growth

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

Diagnostics ◽

10.3390/diagnostics11050749 ◽

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.

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

Antioxidants ◽

10.3390/antiox10101505 ◽

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.

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