RESUMEN
PURPOSE: There is considerable information regarding the medical and cognitive aspects of Klinefelter syndrome yet little research regarding its psychosocial impact. This study investigates the personal impact of Klinefelter syndrome and the influence of age at diagnosis, clinical, social, and demographic factors on adult quality of life outcomes. METHODS: Men from across Australia, diagnosed with KS at different ages, were recruited through multiple sources. Participants completed a questionnaire assessing subjective well-being, body image, self-esteem, mental health, social support, and general health. RESULTS: Eighty-seven individuals self-completed the questionnaire. All outcomes were much poorer for the study population than for the general male population. Individuals diagnosed later in life reported many of the same symptoms as those diagnosed at younger ages. Employment status, social support, and phenotypic features were the strongest predictors of psychosocial outcomes. Age at diagnosis was not as influential because it did not correlate with phenotypic severity score. CONCLUSION: This is the first quantitative study to show Klinefelter syndrome has a significant personal impact. Men diagnosed with Klinefelter syndrome later in life reported similar difficulties as those at younger ages, suggesting that they would benefit from early detection and intervention. Understanding factors influencing this can assist in providing adequate services to individuals with Klinefelter syndrome, their partners, families, and the health professionals caring for them.
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Síndrome de Klinefelter/psicología , Calidad de Vida/psicología , Clase Social , Encuestas y Cuestionarios , Adulto , Anciano , Australia , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Adulto JovenRESUMEN
OBJECTIVE: To determine the prevalence and diagnosis rates of Klinefelter syndrome (KS) in Victoria, Australia, and compare these to previous international findings. DESIGN, SETTING AND PARTICIPANTS: A Victorian population-based descriptive study of all cytogenetic examinations resulting in a diagnosis of KS, including prenatal diagnoses from 1986 to 2006 and postnatal diagnoses from 1991 to 2006. MAIN OUTCOME MEASURES: Birth prevalence and diagnosis rates of KS. RESULTS: The birth prevalence of KS in Victoria is estimated to be 223 per 100,000 males (95% CI, 195-254), with about 50% of cases remaining undiagnosed. CONCLUSIONS: KS may be occurring more frequently than has been reported previously, yet many cases remain undiagnosed. Our results highlight the need for increased awareness leading to timely detection.
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Síndrome de Klinefelter/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Cariotipificación , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Persona de Mediana Edad , Diagnóstico Prenatal/estadística & datos numéricos , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Lipopolysaccharide (LPS) delivered acutely to the ovine fetus induces cerebral white matter injury and brain inflammation. N-acetyl cysteine (NAC) is potentially neuroprotective as it blocks the production of inflammatory cytokines and increases glutathione levels; however, it is unknown whether NAC affects the physiological status of the fetus already exposed to an inflammatory environment. OBJECTIVES: Our objective was to determine whether NAC influences the physiological effects of LPS exposure in the ovine fetus. METHODS: Catheterized fetal sheep underwent one of four treatments (saline, n = 6; LPS, n = 6; LPS + NAC, n = 6; NAC, n = 3) on 5 consecutive days from 95 days of gestation (term approximately 147 days). Fetal arterial pressure and heart rate were recorded and blood samples collected. RESULTS: LPS administration resulted in fetal hypoxemia and hypotension; simultaneous treatment with NAC exacerbated these effects and induced polycythemia. NAC treatment alone had no effect on the fetus. CONCLUSION: In the presence of LPS, NAC compromises fetal physiological status, suggesting that it may not be a suitable antenatal treatment for a fetus with evidence of inflammation.
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Acetilcisteína/farmacología , Antiinflamatorios no Esteroideos/farmacología , Feto/efectos de los fármacos , Hipotensión/inducido químicamente , Hipoxia/inducido químicamente , Lipopolisacáridos/toxicidad , Policitemia/inducido químicamente , Animales , Dióxido de Carbono/metabolismo , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Feto/metabolismo , Feto/fisiopatología , Edad Gestacional , Hemodinámica/efectos de los fármacos , Hipotensión/metabolismo , Hipotensión/fisiopatología , Hipoxia/metabolismo , Hipoxia/fisiopatología , Oximetría , Oxígeno/metabolismo , Policitemia/metabolismo , OvinosRESUMEN
Previous studies have shown that intrauterine growth restriction (IUGR) can impair nephrogenesis, but uncertainties remain about the importance of the gestational timing of the insult and the effects on the renal renin-angiotensin system (RAS). We therefore hypothesized that induction of IUGR during late gestation alters the RAS, and this is associated with a decrease in nephron endowment. Our aims were to determine the effects of IUGR induced during the later stages of nephrogenesis on 1) nephron number; 2) mRNA expression of angiotensin AT(1) and AT(2) receptors, angiotensinogen, and renin genes in the kidney; and 3) the size of maculae densae. IUGR was induced in fetal sheep (n = 7) by umbilical-placental embolization from 110 to 130 days of the approximately 147-day gestation; saline-infused fetuses served as controls (n = 7). Samples of cortex from the left kidney were frozen, and the right kidney was perfusion fixed. Total kidney volume, nephron number, renal corpuscle volume, total maculae densae volume, and the volume of macula densa per glomerulus were stereologically estimated. mRNA expression of AT(1) and AT(2) receptors, angiotensinogen, and renin in the renal cortex was determined. In IUGR fetuses at 130 days, body and kidney weights were significantly reduced and nephron number was reduced by 24%. There was no difference in renin, angiotensinogen, or AT(1) and AT(2) receptor mRNA expression levels in the IUGR kidneys compared with controls. We conclude that fetal growth restriction late in nephrogenesis can lead to a marked reduction in nephron endowment but does not affect renal corpuscle or macula densa size, or renal RAS gene expression.
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Retardo del Crecimiento Fetal/fisiopatología , Feto/fisiología , Riñón/embriología , Riñón/metabolismo , Sistema Renina-Angiotensina/fisiología , Angiotensina II/sangre , Angiotensinógeno/biosíntesis , Angiotensinógeno/genética , Animales , Peso Corporal/fisiología , Índices de Eritrocitos , Femenino , Peso Fetal/fisiología , Expresión Génica , Edad Gestacional , Nefronas/fisiología , Tamaño de los Órganos/fisiología , Embarazo , ARN Mensajero/biosíntesis , Receptor de Angiotensina Tipo 1/biosíntesis , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 2/biosíntesis , Receptor de Angiotensina Tipo 2/genética , Renina/biosíntesis , Renina/sangre , Renina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , OvinosRESUMEN
There is now extensive evidence suggesting that intrauterine perturbations are linked with an increased risk of developing cardiovascular disease. Human epidemiological studies, supported by animal models, have demonstrated an association between low birth weight, a marker of intrauterine growth restriction (IUGR), and adult cardiovascular disease. However, little is known of the early influence of IUGR on the fetal heart and vessels. The aim of this study was to determine the effects of late gestational IUGR on coronary artery function and cardiomyocyte maturation in the fetus. IUGR was induced by placental embolization in fetal sheep from 110 to 130 days of pregnancy (D110-130); term approximately D147; control fetuses received saline. At necropsy (D130), wire and pressure myography was used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in small branches of left descending coronary arteries. Myocardium was dissociated for histological analysis of cardiomyocytes. At D130, IUGR fetuses (2.7 +/- 0.1 kg) were 28% lighter than controls (3.7 +/- 0.3 kg; P = 0.02). Coronary arteries from IUGR fetuses had enhanced responsiveness to the vasoconstrictors, angiotensin II and the thromboxane analogue U46619, than controls (P < 0.01). Endothelium-dependent and -independent relaxations were not different between groups. Coronary arteries of IUGR fetuses were more compliant (P = 0.02) than those of controls. The incidence of cardiomyocyte binucleation was lower in the left ventricles of IUGR fetuses (P = 0.02), suggestive of retarded cardiomyocyte maturation. We conclude that late gestational IUGR alters the reactivity and mechanical wall properties of coronary arteries and cardiomyocyte maturation in fetal sheep, which could have lifelong implications for cardiovascular function.
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Diferenciación Celular/fisiología , Vasos Coronarios/fisiopatología , Retardo del Crecimiento Fetal/fisiopatología , Miocitos Cardíacos/fisiología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Angiotensina II/farmacología , Animales , Bradiquinina/farmacología , Diferenciación Celular/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/embriología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Femenino , Corazón/embriología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Miocitos Cardíacos/citología , Embarazo , Ovinos , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes. Pregnant sheep were infused intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116, 117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days). Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were measured before and after each infusion. Compared with controls, ethanol exposure reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I (-35%) at 30 h, and decreased fetal plasma IGF-II (-28%) from 24 to 54 h after the first infusion. Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We conclude that suppression of maternal and fetal IGF abundance may contribute to fetal growth restriction induced by acute or binge ethanol exposure.
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Etanol/efectos adversos , Intercambio Materno-Fetal/efectos de los fármacos , Preñez/efectos de los fármacos , Somatomedinas/análisis , Animales , Etanol/administración & dosificación , Femenino , Sangre Fetal/química , Retardo del Crecimiento Fetal/inducido químicamente , Peso Fetal/efectos de los fármacos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/análisis , Embarazo , Preñez/sangre , OvinosRESUMEN
OBJECTIVE: Intrauterine infection has been linked to brain injury in human infants, although the mechanisms are not fully understood. We recently showed that repeated acute exposure of preterm fetal sheep to bacterial endotoxin (lipopolysaccharide [LPS]) results in fetal hypoxemia, hypotension, increased systemic proinflammatory cytokines, and brain damage, including white matter injury. However, it is not clear whether this injury is caused by reduced cerebral oxygen delivery or inflammatory pathways independent of hypoxia. The aim of the present study was to determine the effects on the fetal brain and placenta of a chronic intrauterine inflammatory state, induced by LPS infusion into the fetal circulation, a model that did not cause hypoxia. METHODS: At 0.65 of term, eight catheterized fetal sheep received intravenous infusions of LPS (5 to 15 mug) over 5 days; control fetuses received saline. Fetal physiologic responses were monitored throughout the infusion. Fetal brain and placental tissues were examined histologically 6 days after the conclusion of the infusion. RESULTS: LPS infusions did not result in physiologically significant alterations to fetal blood gases or mean arterial pressure; however, plasma proinflammatory cytokine levels were elevated. Following LPS exposure there was no difference in fetal body or brain weights (P >.05); placental weight was reduced (P <.05), consistent with reduced placentome cross-sectional area (P <.05). In the cerebral hemispheres subcortical white matter injury was present in six LPS-exposed fetuses and included axonal damage, microgliosis, oligodendrocyte injury, and increased beta amyloid precursor protein (beta-APP) expression. CONCLUSIONS: Chronic, systemic exposure of the fetus to LPS resulted in fetal brain damage in the absence of hypoxemia or hypotension, although the resulting injury was less severe than following repeated acute exposure.
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Encefalopatías/veterinaria , Encéfalo/embriología , Lipopolisacáridos/administración & dosificación , Enfermedades de las Ovejas/inducido químicamente , Ovinos/embriología , Precursor de Proteína beta-Amiloide/análisis , Animales , Axones/patología , Encefalopatías/metabolismo , Encefalopatías/patología , Citocinas/sangre , Femenino , Sangre Fetal , Hipoxia/inducido químicamente , Hipoxia/veterinaria , Oligodendroglía/patología , Placenta/efectos de los fármacos , EmbarazoRESUMEN
As the transition to extrauterine life at birth alters the proportions of type I and II alveolar epithelial cells (AECs), our aim was to determine the effect of mild preterm birth on AECs and surfactant protein (SP) gene expression. Preterm lambs were born at approximately 133 d of gestational age (DGA); controls were born at term (approximately 147 DGA). Lungs were collected from preterm lambs at term-equivalent age (TEA; approximately 2 wk after preterm birth) and 6 wk post-TEA. Control lung tissue was collected from fetuses (at 132 DGA), as well as from lambs at approximately 6 h (normal term) and 2, 6, and 8 wk of postnatal age (PNA). In controls, the proportion of type I AECs decreased from 65.1 +/- 3.9% at term to 50.9 +/- 3.3%, while the proportion of type II AECs increased from 33.7 +/- 3.9% to 48.5 +/- 3.3% at 6 wk PNA. At 2 wk after preterm birth, the proportions of type I and II AECs were similar in preterm lambs compared to 132-d fetal levels and term controls but differed from control values at 2 wk PNA; differences between control and preterm lambs persisted at 8 wk PNA. At approximately 2 wk after preterm birth, SP-A and SP-B, but not SP-C, mRNA levels were significantly reduced in preterm lambs compared with term controls, but these differences did not persist at 2 and 6 wk PNA. We conclude that mild preterm birth alters the normal postnatal changes in type I and II cell proportions but does not severely affect SP gene expression.
Asunto(s)
Nacimiento Prematuro/metabolismo , Alveolos Pulmonares/citología , Proteínas Asociadas a Surfactante Pulmonar/metabolismo , Animales , Animales Recién Nacidos , Diferenciación Celular/genética , Células Epiteliales/química , Células Epiteliales/citología , Nacimiento Prematuro/genética , Alveolos Pulmonares/química , Alveolos Pulmonares/metabolismo , Proteínas Asociadas a Surfactante Pulmonar/genética , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Oveja DomésticaRESUMEN
Low birth weight (LBW) as a result of restricted fetal growth increases the risk for later metabolic diseases and adiposity. However the relationship between LBW and postnatal growth and adult body composition has not been fully investigated. We have used sheep to determine the effects of LBW on postnatal growth and body composition at maturity. LBW was induced by twinning and placental embolization. At birth, LBW lambs were 38% lighter than controls (2.8 +/- 0.2 vs 4.4 +/- 0.3 kg, P<0.05), but had caught up in bodyweight by 8 weeks after birth. At approximately 2.3 years, bodyweights were not different between groups, but there were reductions in absolute (-8%) and relative (-17%) brain weights of LBW sheep (P<0.05) compared to controls. X-ray absorptiometry showed that the mature LBW sheep, compared to controls, had greater amounts of lean muscle (38.1 +/- 1.3 vs 35.3 +/- 0.5 kg, P<0.05) and tended to have more body fat (12.2 +/- 1.2 vs 9.6 +/- 0.9 kg; P=0.1); at autopsy abdominal fat mass was greater in LBW sheep (3.06 +/- 0.26 vs 2.20 +/- 0.25 kg, P<0.05). Plasma leptin concentrations were not different between groups. We conclude that, in sheep, LBW is associated with early postnatal catch-up in body weight, but body composition is permanently altered such that, relative to controls, adiposity is increased and brain weight is decreased.
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Tejido Adiposo/metabolismo , Peso al Nacer , Encéfalo/patología , Absorciometría de Fotón , Animales , Composición Corporal , Constitución Corporal , Peso Corporal , Encéfalo/metabolismo , Leptina/metabolismo , Tamaño de los Órganos , Ovinos , Factores de Tiempo , Aumento de PesoRESUMEN
Lung hypoplasia (LH) is a serious cause of neonatal compromise, but little is known of its functional effects on the pulmonary circulation. Our aim was to characterize birth-related changes in the pulmonary circulation of newborn lambs with LH and to compare them with alterations in respiratory function. LH was induced in six ovine fetuses by the creation of a tracheo-amniotic shunt as well as amniotic fluid drainage starting at 105.6+/-1.5 (mean+/-SEM) days of gestation (term approximately 147 d). At 139.9+/-0.3 d, fetuses were exteriorized under anesthesia to implant vascular catheters and an ultrasonic flow probe around the left pulmonary artery. The lambs then were delivered and ventilated for 2 h, during which systemic and pulmonary artery pressures, left pulmonary blood flow, and measures of respiratory function were recorded. At autopsy, lungs were weighed and volume was measured at 20 cm H2O. In LH lambs, lung weight was 25% lower and respiratory system compliance was 30% lower than in controls. Mean pulmonary blood flow in LH lambs was 42% lower and pulmonary vascular resistance was 138% higher than in controls. Morphometry showed that volume density of pulmonary arteries in LH was 30% lower than in controls. We conclude that, in this LH model, changes in ventilatory indices were proportional to the change in lung size, whereas changes in the pulmonary circulation were greater than the change in lung size and were associated with reduced density of pulmonary arteries. LH severely impairs normal adaptation of the pulmonary circulation in the perinatal period.
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Pulmón/irrigación sanguínea , Pulmón/patología , Circulación Pulmonar/fisiología , Animales , Animales Recién Nacidos , Femenino , Edad Gestacional , Pulmón/anatomía & histología , Pulmón/fisiología , Rendimiento Pulmonar , Embarazo , Arteria Pulmonar/anatomía & histología , Pruebas de Función Respiratoria , Fenómenos Fisiológicos Respiratorios , Oveja DomésticaRESUMEN
Chronic placental insufficiency (CPI) has the potential to affect fetal brain development and to cause brain injury. Our aim was to determine the effects of exposure to CPI during late gestation on brain and retinal structure and brain neurotrophin expression 8 weeks after birth. Six fetal sheep were exposed to CPI, induced by umbilico-placental embolization, from 120 days of gestation until term (approximately 147 days) such that fetal arterial oxygen saturation (SaO2) was reduced by approximately 50%. Nine untreated animals served as controls. During CPI, fetal arterial PO2, SaO2, pH, and growth were reduced (p < 0.05); these animals remained small at 8 weeks after birth. Structural abnormalities were present in the brains and retinae of all CPI-exposed lambs. There was a reduction in retinal width and in the number of retinal tyrosine hydroxylase-immunoreactive dopaminergic amacrine cells (p < 0.05). In the dorsal hippocampus the combined width of strata oriens and pyramidale was significantly reduced (p < 0.05). In the cerebellum there was a significant reduction (p = 0.05) in cerebellar cross-sectional area, most notably in the inner granule cell layer, and a reduction (p < 0.05) in immunoreactivity for the cytoskeletal protein neurofilament-200 in the white matter. Gliosis was present in either the cerebral white matter or cerebellum in all animals and degeneration was seen around blood vessels in 4/6 umbilico-placental embolization animals. There were reductions in brain-derived neurotrophic factor immunoreactivity in the hippocampus (p < 0.05) and tyrosine kinase B immunoreactivity in the cerebellum (p < 0.05). This study shows that late gestational CPI affects morphology and neurotrophin expression of the postnatal brain. These alterations in the brain can apparently persist from fetal life or become established after birth; some changes that were present in the fetus at term did not persist into postnatal life.
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Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Insuficiencia Placentaria/complicaciones , Retina/embriología , Retina/crecimiento & desarrollo , Animales , Encéfalo/patología , Dióxido de Carbono/sangre , Femenino , Gliosis/etiología , Gliosis/patología , Inmunohistoquímica , Degeneración Nerviosa/etiología , Degeneración Nerviosa/patología , Factores de Crecimiento Nervioso/biosíntesis , Oxígeno/sangre , Embarazo , Retina/patología , OvinosRESUMEN
Our aim was to determine the effects of chronic placental insufficiency (CPI) during late gestation on the expression of neurotrophic factors and their receptors in the hippocampus and cerebellum in the near-term fetus. Structural alterations were also assessed in these brain regions. CPI was induced in eight fetal sheep by umbilicoplacental embolization (UPE) from 120 to 140 days of gestation (term approximately 147d) such that fetal arterial O2 saturation (SaO2) was maintained at approximately 50% of pre-UPE values. Five non-UPE fetuses served as controls. UPE resulted in fetal hypoxemia, hypoglycaemia, and growth restriction. In hippocampi from UPE fetuses, there were reductions in the optical density (OD) of the immunoreactivity (IR) of brain-derived neurotrophic factor (BDNF) protein within the mossy fibre collaterals of the polymorphic layer and in stratum lucidum (p<0.05); there was no consistent effect on tyrosine-related kinase (Trk) B receptor or neurotrophin-3 (NT-3) expression. Within the cerebellum, there was an increase in BDNF-IR (p<0.05) in the molecular layer; however, Trk B-IR and NT-3-IR were unaltered. There were no significant alterations to the structural parameters measured in the hippocampus. We conclude that CPI in late gestation affects the expression of BDNF in the fetal hippocampus and cerebellum, but these changes do not have a well-defined relationship to structural outcome.
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Cerebelo/metabolismo , Hipocampo/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Insuficiencia Placentaria/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Cerebelo/citología , Cerebelo/embriología , Femenino , Feto/metabolismo , Hipocampo/citología , Hipocampo/embriología , Inmunohistoquímica , Neurotrofina 3/biosíntesis , Embarazo , Células de Purkinje/metabolismo , Receptor trkB/biosíntesis , OvinosRESUMEN
OBJECTIVE: Previous studies on the effects of umbilical cord occlusion (UCO) on the fetal brain have focused on short-term alterations, and in most cases have used only subjective techniques to evaluate brain injury. Our aim was to assess quantitatively the persistent consequences of UCO on the developing brain; we also examined the retina. METHODS: We subjected fetal sheep to a single episode of UCO at 126 days of gestation (term approximately 147 days) to induce at least 10 minutes of isoelectric fetal electrocorticogram (ECoG). RESULTS: UCO resulted in fetal asphyxia and transient mild alterations in fetal mean arterial pressure (MAP). UCO did not result in significant injury to the developing brain or retina when assessed 15 days after the insult. There was no change in the endogenous expression of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, nor was there a significant loss of CA1 hippocampal pyramidal cells. However, this insult did result in subtle neuropathologic alterations in the brain, including a reduction in the weight of the cerebral hemispheres, an increase in the areal density of cerebellar Purkinje cells, and enlarged perivascular spaces around blood vessels and inflammatory cells in the cerebral white matter. UCO did not affect the thickness of the central or peripheral retina or the numbers of retinal dopaminergic, cholinergic, and nitrergic amacrine cells. CONCLUSIONS: Thus, while 10 minutes of UCO did not result in overt injury to the fetal brain or retina, the observed changes in the fetal brain suggest altered growth of neural processes, which may contribute to neurologic deficits postnatally or to increased vulnerability of the brain to later insults during either the remainder of gestation or after birth.
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Encéfalo/embriología , Retina/embriología , Cordón Umbilical/patología , Enfermedades Vasculares/complicaciones , Animales , Asfixia Neonatal/fisiopatología , Presión Sanguínea , Encéfalo/patología , Lesiones Encefálicas/etiología , Factor Neurotrófico Derivado del Encéfalo/análisis , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Femenino , Desarrollo Fetal , Hipocampo/química , Humanos , Recién Nacido , Embarazo , Retina/patología , OvinosRESUMEN
Hypoxia and nutrient restriction during gestation restrict fetal growth and alter lung development. As elastin is intimately involved in lung development, our aim was to assess pulmonary elastin synthesis and deposition following intrauterine growth restriction (IUGR) induced by umbilicoplacental embolization (UPE). Pulmonary tropoelastin expression and elastin content were examined at 128 days (5 days UPE) and 140 days (20 days UPE) of the 147- days gestation and at 8 weeks and 2.3 years after birth (both approximately 27 days UPE) in sheep. UPE induced hypoxemia, hypoglycemia, and fetal growth restriction but did not affect pulmonary tropoelastin mRNA levels or elastin deposition at any age; furthermore, elastin content was unaltered apart from being lower at 140 days. The authors conclude that hypoxemia and undernutrition associated with IUGR do not affect elastin synthesis and deposition in fetal lungs; alterations in lung structure following IUGR must have other causes.
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Elastina/biosíntesis , Retardo del Crecimiento Fetal/embriología , Retardo del Crecimiento Fetal/metabolismo , Pulmón/embriología , Pulmón/metabolismo , Ovinos/embriología , Ovinos/metabolismo , Animales , Oclusión con Balón , Femenino , Edad Gestacional , Microesferas , Placenta/irrigación sanguínea , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tropoelastina/genéticaRESUMEN
Low birth weight is associated with adult-onset diseases including hypertension and renal disease; altered renal development after intrauterine growth restriction (IUGR) may underlie such prenatal programming. Our aim was to investigate nephron endowment and renal filtration surface area in fetal sheep in which IUGR resulted from late gestational umbilico-placental embolization (UPE) or natural twinning. UPE was performed between 120 and 140 d of gestation (term approximately 147 d). At autopsy (140 d), body weights of UPE and twin fetuses were, respectively, 34% and 28% lower than controls. Kidneys were sampled using a smooth fractionator approach and glomerular number was estimated using a physical disector/fractionator technique. Glomerular capillary length and filtration surface area were estimated using unbiased stereological techniques. Although relative kidney weights (grams per kilogram body weight) were not different between groups, nephron endowment was 40% lower in twin fetuses compared with controls (34.3 +/- 10.6 x 10(4) and 55.9 +/- 19.8 x 10(4), respectively; p < 0.05); UPE did not alter nephron number (50.7 +/- 13.2 x 10(4)). There was no difference in the glomerular capillary length or surface area between the UPE and control fetuses. IUGR due to twinning leads to reduced nephron endowment whereas late gestational IUGR does not, suggesting that reduced nephron endowment is dependent on the timing of the growth restriction. Our findings demonstrate that reduced birth weight per se does not necessarily imply reduced nephron endowment.
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Retardo del Crecimiento Fetal/patología , Tasa de Filtración Glomerular , Riñón/embriología , Nefronas/embriología , Animales , Peso al Nacer , Capilares/patología , Peso Fetal , Humanos , Riñón/irrigación sanguínea , Riñón/patología , Nefronas/metabolismo , Tamaño de los Órganos , Placenta/patología , Ovinos , Factores de Tiempo , Gemelos , Cordón Umbilical/patologíaRESUMEN
We have previously shown that fetal growth restriction (FGR) during late gestation in sheep affects lung development in the near-term fetus and at 8 wk after birth. In the present study, our aim was to determine the effects of FGR on the structure of the lungs at 2 y after birth; our hypothesis was that changes observed at 8 wk after birth would persist until maturity. FGR was induced in sheep by umbilicoplacental embolization, which was maintained from 120 d until delivery at term (approximately 147 d); birth weights of FGR lambs were 41% lower than in controls. At 2 y after birth, body and lung weights were not different, but there were 28% fewer alveoli and alveoli were significantly larger than in controls; hence there was a 10% reduction in the internal surface area relative to lung volume in FGR sheep compared with controls. The lungs of FGR sheep, compared with controls, had thicker interalveolar septa as a result of increased extracellular matrix deposition; the alveolar blood-air barrier was also thicker, largely because of an 82% increase in basement membrane thickness. These changes are qualitatively similar to those observed at 8 wk. Our data show that structural alterations in the lungs induced by FGR that were apparent at 8 wk were still evident at 2 y after birth, indicating that FGR may result in permanent changes in the structure of the lungs of the offspring and may affect respiratory health and lung aging later in life.
Asunto(s)
Retardo del Crecimiento Fetal/patología , Retardo del Crecimiento Fetal/fisiopatología , Alveolos Pulmonares/crecimiento & desarrollo , Alveolos Pulmonares/patología , Factores de Edad , Animales , ADN/metabolismo , Elastina/metabolismo , Femenino , Mediciones del Volumen Pulmonar , Microscopía Electrónica , Tamaño de los Órganos , Oxígeno/sangre , Embarazo , Proteínas/metabolismo , Alveolos Pulmonares/embriología , Intercambio Gaseoso Pulmonar , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Mucosa Respiratoria/ultraestructura , OvinosRESUMEN
The aim of this study was to determine the effects of foetal growth restriction on the retina after birth. Foetal growth restriction (FGR) was induced via umbilico-placental embolization (UPE) in ewes from 120 days of pregnancy until term (term approximately 147 days); controls were not exposed to UPE. Lambs were delivered and raised until 2 years of age when retinas were collected and processed for structural and neurochemical analysis. The foetuses exposed to UPE were hypoxemic and at birth were growth restricted. In 2-year-old FGR sheep, the total thickness of the retina and the number of tyrosine hydroxylase immunoreactive dopaminergic amacrine cells were reduced compared to controls (P < 0.05). It is concluded that restricted foetal growth leads to long-term structural and neurochemical changes in the retina. Of particular interest are the alterations to dopaminergic amacrine cell numbers, as alterations in this population may affect contrast sensitivity and have implications for the alterations in vision observed in very low birthweight infants.
Asunto(s)
Animales Recién Nacidos , Retardo del Crecimiento Fetal/etiología , Retardo del Crecimiento Fetal/patología , Insuficiencia Placentaria/complicaciones , Retina/patología , Células Amacrinas/enzimología , Animales , Peso Corporal , Enfermedad Crónica , Femenino , Retardo del Crecimiento Fetal/sangre , Retardo del Crecimiento Fetal/enzimología , Gases/sangre , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ovinos , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Intrauterine infection has been linked to neurologic injury in preterm infants. However, a reproducible model of white matter injury in the preterm fetus in a long gestation species that can be monitored in utero is currently unavailable. Thus, our objective was to determine the effects of bacterial endotoxin (lipopolysaccharide, LPS) on physiologic and inflammatory responses and brain structure in the preterm ovine fetus. At 0.7 of gestation, six catheterized fetuses received three to five intravenous injections of LPS (1 micro g/kg) over 5 d; seven fetuses served as controls. Fetal responses were monitored and brain tissue examined 10-11 d after the initial LPS injection. After LPS on d 1 and 2, fetuses became transiently hypoxemic and hypotensive and blood IL-6 levels were increased, but these responses were smaller or absent after subsequent LPS exposures. Neural injury was observed in all LPS-exposed fetuses, most prominently in the cerebral white matter. Injury ranged from diffuse subcortical damage to periventricular leukomalacia, and in the brainstem the cross-sectional area of the corticospinal tract was reduced by 30%. Thus, repeated exposure of the preterm ovine fetus to LPS causes neuropathology resembling that of cerebral palsy and provides a robust model for exploring the etiology, prevention, and treatment of white matter damage.
Asunto(s)
Lesiones Encefálicas/etiología , Feto/efectos de los fármacos , Lipopolisacáridos/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Lesiones Encefálicas/patología , Citocinas/sangre , Modelos Animales de Enfermedad , Femenino , Sangre Fetal/metabolismo , Feto/fisiología , Edad Gestacional , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Recién Nacido , Inflamación/etiología , Inflamación/patología , Leucomalacia Periventricular/etiología , Lipopolisacáridos/administración & dosificación , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Tamaño de los Órganos/efectos de los fármacos , Embarazo , OvinosRESUMEN
BACKGROUND: Oligohydramnios, a severe reduction in the volume of amniotic fluid, is associated with fetal lung hypoplasia but underlying processes are unclear. Studies in sheep suggest that oligohydramnios may lead to lung hypoplasia by causing increased flexion of the fetal spine, but this has not been demonstrated in the human, which has a different uterine anatomy. AIMS: Our aims were to quantify spinal flexion in the human fetus and to determine the relationship between oligohydramnios and the degree of spinal flexion. SUBJECTS AND METHODS: In 35 pregnancies, we used ultrasonography to assess amniotic fluid volume and to image the fetal spine so as to provide an index of mean spinal radius between the upper thoracic and lumbar spine. In 17 pregnancies with evidence of oligohydramnios resulting from premature rupture of membranes (mean +/- SEM gestation 28.8 +/-1.4 weeks), the mean radius of fetal spinal curvature between the upper thorax and sacrum was compared with values from 18 control fetuses with normal amounts of amniotic fluid (at 28.9 +/- 1.6 weeks). RESULTS: In each fetus, the spine could be imaged and the mean radius of curvature calculated. Oligohydramnios was associated with a significantly increased degree of fetal spinal flexion compared to controls. CONCLUSION: In human pregnancy, oligohydramnios is associated with increased flexion of the fetal spine, which is likely due to reduced uterine volume. This could contribute to the development of fetal lung hypoplasia, fetal immobility and other fetal anomalies.
Asunto(s)
Enfermedades Fetales/etiología , Oligohidramnios/complicaciones , Curvaturas de la Columna Vertebral/etiología , Columna Vertebral/embriología , Puntaje de Apgar , Presentación de Nalgas , Femenino , Rotura Prematura de Membranas Fetales/complicaciones , Edad Gestacional , Humanos , Pulmón/anomalías , Embarazo , Resultado del Embarazo , Ultrasonografía PrenatalRESUMEN
Epidemiologic studies suggest that intrauterine growth restriction (IUGR) can lead to impaired lung function, yet little information exists on the effects of IUGR on airway development. Our objectives were to characterize morphometrically effects of IUGR on airway structure in the fetus and to determine whether alterations persist into postnatal life. We used two groups of sheep, each with appropriate controls; a fetal group was subjected to IUGR by restriction of placental function from 120 to 140 d (term approximately 147 d), and a postnatal group, killed 8 wk after birth, was subjected to IUGR from 120 d to birth at term. In both fetuses and postnatal lambs, IUGR did not alter lung weight relative to body weight. In IUGR fetuses, the luminal areas and basement membrane perimeters of the trachea and larger bronchi (generations 0-8, trachea = 0) were smaller than in controls. Airway wall areas, relative to basement membrane perimeters, were reduced in IUGR fetuses compared with controls, largely due to reduced areas of cartilage and epithelium. At 8 wk after birth, there were no significant differences in airway dimensions between IUGR and control lambs. However, the number of profiles of bronchial submucosal glands, relative to basement membrane perimeters, was lower in IUGR lambs than in controls and the area of epithelial mucin was increased. We conclude that restriction of fetal growth during late gestation impairs the growth of bronchial walls that could affect airway compliance in the immediate postnatal period. Although airway growth deficits are reversed by 8 wk, alterations in mucus elements persist.