Malformations in offspring of diabetic rats: Morphometric analysis of neural crest-derived organs and effects of maternal vitamin E treatment

Simán, C Martin; Groot, Adriana C. Gittenberger‐de; Wisse, Bert; Eriksson, Ulf J.

doi:10.1002/(sici)1096-9926(200005)61:5<355::aid-tera7>3.3.co;2-n

Cited by 32 publications

(55 citation statements)

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“…These low incidence rates prevented breaking the data down by defect for statistical analysis, with the exception of shortened mandible and maxillae, which were by far the most common lesions encountered. The micrognathia we observed in the diabetic mice has also been associated with maternal diabetes in rats (Siman et al, 2000). Hyperglycemia could be inhibiting the proliferation and migration of rhombencephalic neural crest causing a reduction in tissue mass that will form the mandible as suggested by previous reports (Suzuki et al, 1996;Cederberg et al, 2003).…”

Section: Maxillary Lengthsupporting

confidence: 66%

“…Fetuses were placed in lateral recumbency and were measured with an ocular micrometer using a Nikon SMZ stereomicroscope to determine mandibular, maxillary, and crown to rump lengths. Mandibular and maxillary measurements were determined as described by Siman et al (2000). Measurements were taken from the rostral most point on the muzzle or chin to the base of the skull.…”

Section: Methodsmentioning

confidence: 99%

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Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Hrubec

Prater

Toops

et al. 2005

Birth Defects Research Pt B

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BACKGROUND: Maternal diabetes can induce a number of developmental abnormalities in laboratory animals and humans, including facial deformities and defects in neural tube closure. The incidence of birth defects in newborns of diabetic women is approximately 3–5 times higher than among non‐diabetics. In mice, non‐specific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes induced neural tube defects. This study was conducted to determine whether non‐specific maternal immune stimulation could reduce diabetes‐induced craniofacial defects as well. METHODS: Maternal immune function was stimulated before streptozocin (STZ) treatment by maternal footpad injection with Freund's complete adjuvant (FCA), maternal intraperitoneal (i.p.) injection with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), or maternal i.p. injection with interferon‐γ (IFNγ). Streptozocin (200 mg/kg i.p.) was used to induce hyperglycemia (26–35 mmol blood glucose) in female ICR mice before breeding. Fetuses from 12–18 litters per treatment group, were collected at Day 17 of gestation. RESULTS: Craniofacial defects were observed in fetuses from all hyperglycemic groups. The incidence of defects was significantly decreased in fetuses from dams immune stimulated with IFNγ or GM‐CSF. The most common defects were reduced maxillary and mandibular lengths. Both were prevented by maternal stimulation with GM‐CSF. CONCLUSION: Maternal immune stimulation reduced the incidence of diabetic craniofacial embryopathy. The mechanisms for these protective effects are unknown but may involve maternal or fetal production of cytokines or growth factors that protect the fetus from the dysregulatory effects of hyperglycemia. Birth Defects Res Part B 2006. © 2005 Wiley‐Liss, Inc.

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Section: Maxillary Lengthsupporting

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Hrubec

Prater

Toops

et al. 2005

Birth Defects Research Pt B

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“…As in human diabetic pregnancies, malformations in streptozotocin-induced experimental models of diabetes occur mainly in the neural system, heart, and skeleton (Eriksson 2009;Schaefer-Graf et al 2000;Simán et al 2000). Both increased oxidative stress and nitrosative stress are crucial features in diabetes-induced embryopathy and have been characterized in chemical-induced and genetic models of diabetes and even in mild diabetic experimental models (Eriksson et al 2003;Jawerbaum and González 2006;Ornoy 2007).…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

Saito

Damasceno

Dallaqua

et al. 2013

Cell Stress and Chaperones

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We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; nontreated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R0 0.5908, P00.0024; R00.4877, P00.0134, respectively) and the number of malformations per fetus (R 00.6103, P0 0.0015; R 00.4875, P 00.0134, respectively). The antihsp60 IgG concentration was correlated with the number of malformations per fetus (R00.3887, P00.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R00.3999, P00.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes.

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“…We also wanted to measure mRNA levels of GAPDH in embryos subjected to diabetes in vivo or hyperglycemia in vitro. We chose to perform these investigations in an experimental system using rat embryos that have previously displayed skeletal, central nervous system, and cardiac malformations in vivo (26,27), and neural tube closure defects in vitro (28), all of which closely resemble malformations found in human diabetic pregnancy. In addition, we aimed to investigate if the inhibition of GAPDH with iodoacetate (IA) induces a dysmorphogenesis in rat embryos analogous to the maldevelopment caused by high glucose concentration, and whether antioxidants could modulate the putative teratogenic effect of direct GAPDH inhibition as they do with glucose-induced embryonic dysmorphogenesis.…”

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confidence: 99%

Maternal Diabetes In Vivo and High Glucose In Vitro Diminish GAPDH Activity in Rat Embryos

2003

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The aim of the present study was to investigate whether diabetic embryopathy may be associated with the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) resulting from an excess of reactive oxygen species (ROS) in the embryo. Recent demonstrations of enhanced ROS production in mitochondria of bovine aortic endothelial cells exposed to high glucose have supported the idea that the pathogenesis of diabetic complications may involve ROS-induced GAPDH inhibition. We investigated whether a teratogenic diabetic environment also inhibits embryonic GAPDH activity and alters GAPDH gene expression and whether antioxidants diminish such GAPDH inhibition. In addition, we determined whether the inhibition of GAPDH with iodoacetate induces dysmorphogenesis, analogous to that caused by high glucose concentration, and whether antioxidants modulated the putative teratogenic effect of such direct GAPDH inhibition. We found that embryos from diabetic rats and embryos cultured in high glucose concentrations showed decreased activity of GAPDH (by 40 -60%) and severe dysmorphogenesis on gestational days 10.5 and 11.5. GAPDH mRNA was decreased in embryos of diabetic rats compared to control embryos. Supplementing the high-glucose culture with the antioxidant N-acetylcysteine (NAC) increased GAPDH activity and diminished embryonic dysmorphogenesis. Embryos cultured with iodoacetate showed both decreased GAPDH activity and dysmorphogenesis; supplementing the culture with NAC increased both parameters toward normal values. In conclusion, dysmorphogenesis caused by maternal diabetes is correlated with ROS-induced inhibition of GAPDH in embryos, which could indicate that inhibition of GAPDH plays a causal role in diabetic embryopathy. Diabetes

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Malformations in offspring of diabetic rats: Morphometric analysis of neural crest-derived organs and effects of maternal vitamin E treatment

Cited by 32 publications

References 0 publications

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

Maternal Diabetes In Vivo and High Glucose In Vitro Diminish GAPDH Activity in Rat Embryos

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