Intrauterine Growth Restriction in a Rodent Model and Developmental Programming of the Metabolic Syndrome: A Critical Appraisal of the Experimental Evidence

Neitzke, U.; Harder, Thomas; Schellong, Karen; Melchior, Kerstin; Ziska, Thomas; Rodekamp, Elke; Dudenhausen, J. W.; Plagemann, Andreas

doi:10.1016/j.placenta.2007.11.014

Cited by 55 publications

(47 citation statements)

References 38 publications

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“…10,11 Contention exists with regard to the reproducibility of these models. 27 However, consistent observations of IUGR are reported by numerous investigators 10 -12,28,29 ; moreover, similar phenotypic outcomes, such as a reduction in nephron number, have been observed in response to placental insufficiency, an observation that is not species specific. 29 -32 Overnutrition as a nutritional insult during fetal life also programs metabolic and cardiovascular dysfunction, [33][34][35] implications critical because of the increased prevalence of obesity.…”

Section: Animal Models Of Nutritional Manipulation During Fetal Lifesupporting

confidence: 62%

Developmental Programming of Hypertension

2008

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Section: Animal Models Of Nutritional Manipulation During Fetal Lifesupporting

confidence: 62%

Developmental Programming of Hypertension

2008

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“…[21][22][23] It is still used today, especially to study these brain injuries. [21][22][23][24] For this study, 32 female rats were anaesthetised on day 16 of pregnancy by intraperitoneal injection of 2% xylazine (Rompum; Bayer, Puteaux, France) and ketamine (Imalgène; Rhô ne Mérieux, Lyon, France). The abdomen was shaved and a midline laparotomy incision was made under aseptic conditions.…”

Section: Animal Modelmentioning

confidence: 99%

SPIO‐enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction

Deloison

Siauve

Aimot

et al. 2012

BJOG

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Objective To assess placental perfusion with magnetic resonance imaging (MRI) and superparamagnetic iron oxide (SPIO) in a rat model of intrauterine growth restriction (IUGR).Design Experimental animal study.Setting The study complied with US National Institutes of Health recommendations for animal care.Population Thirty-two rats at day 16 of gestation underwent surgical ligation of the left uterine vessel to induce IUGR.Methods Eighteen rats were examined by MRI 3 days later, after bolus injection of ferucarbotran.Main outcome measure Signal intensities were measured in the maternal left ventricle and in the placentas of the two horns. Quantitative microcirculation parameters were calculated and compared between the placentas of the two horns.Results Fifty-four kinetic curves of placental perfusion were obtained in 11 rats. The mean placental blood flow was significantly lower in the ligated horns than in the normal horns (108.1 versus 159.4 ml/minute/100 ml, p = 0.0004). The mean fractional volume of the maternal vascular placental compartment did not differ significantly between the pathological (42.8%) and normal placentas (39.2%).Conclusions Placental perfusion, including changes during experimental IUGR, can be measured in rats by using MRI with SPIO. These findings could have implications for human studies of placental microcirculation and for the management of disorders related to placental dysfunction.

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“…UGR, a disease complex that is increasing at epidemic rates worldwide, has been linked to metabolic syndrome, including insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver (1)(2)(3). Insulin resistance is an essential aspect of metabolic syndrome, and numerous cytokines reportedly contribute to the development of these disorders (4); however, the molecular mechanisms leading to the development of metabolic syndrome in intrauterine growth retardation (IUGR) -born adults is still poorly understood.…”

mentioning

confidence: 99%

The Influence of Down-Regulation of Suppressor of Cellular Signaling Proteins by RNAi on Glucose Transport of Intrauterine Growth Retardation Rats

et al. 2011

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Intrauterine growth retardation (IUGR) has been linked to metabolic syndrome including insulin resistance, and overexpression of suppressors of cytokine signaling (SOCSs) proteins is thought to be associated with increased whole-body insulin sensitivity. The insulin-resistant IUGR rat model was established by maternal food restriction (about 30% of the normal rats). The weight, length, and homeostasis model assessment of insulin resistance (HOMA-IR) of IUGR-born rats was higher than the control group. Insulin receptor substrate (IRS)-1 expression decreased, whereas SOCS-1 and SOCS-3 increased in the skeletal muscle of IUGR rats compared with the control group. The recombination plasmids PGPU6/GFP/Neo-SOCS-1small hairpin RNA (shRNA) and PGPU6/GFP/Neo-SOCS-3shRNA were transfected into skeletal muscle cells, and the shRNAs efficiently inhibited the expression of SOCS-1 and SOCS-3. Insulin-stimulated glucose transporter-4 (GLUT4) translocation was also dramatically increased. In conclusion, these data provide additional information on the mechanism of insulin resistance associated with IUGR. Down-regulation of SOCS-1 and SOCS-3 ameliorates the capacity of glucose transport and provides a potential gene therapy approach to managing metabolic syndrome. (Pediatr Res 69: 497-503, 2011) I UGR, a disease complex that is increasing at epidemic rates worldwide, has been linked to metabolic syndrome, including insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver (1-3). Insulin resistance is an essential aspect of metabolic syndrome, and numerous cytokines reportedly contribute to the development of these disorders (4); however, the molecular mechanisms leading to the development of metabolic syndrome in intrauterine growth retardation (IUGR) -born adults is still poorly understood.Suppressors of cytokine signaling (SOCSs) are thought to participate in negative feedback loops in cytokine signaling via various mechanisms. A promoter polymorphism of the SOCS-3 gene is thought to be associated with increased whole-body insulin sensitivity. One study has shown that overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes (5). Recent studies showed that SOCS-1 knockout mice had lower glucose levels than WTs and that cells derived from the SOCS-1 knockout mice apparently exhibited enhanced insulin signaling. However, it is important to note that determining insulin sensitivity in vivo using SOCS-1 knockout mice is difficult because they die within 3 wk of birth (6).In this study, we investigated basal SOCS-1, SOCS-3, glucose transporter-4 (GLUT4), and insulin receptor substrate (IRS)-1 content in insulin resistance-associated IUGR rats. And on the basis of comparing various features between IUGR and normal models, we hypothesized that downregulation of SOCS-1 and SOCS-3 through small hairpin RNAs (shRNAs) may promote insulin-stimulated GLUT4 translocation in IUGR skeletal muscle cells. MATERIALS ...

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Intrauterine Growth Restriction in a Rodent Model and Developmental Programming of the Metabolic Syndrome: A Critical Appraisal of the Experimental Evidence

Cited by 55 publications

References 38 publications

Developmental Programming of Hypertension

Developmental Programming of Hypertension

SPIO‐enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction

The Influence of Down-Regulation of Suppressor of Cellular Signaling Proteins by RNAi on Glucose Transport of Intrauterine Growth Retardation Rats

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