Somatomedin inhibitors from human serum produce abnormalities in mouse embryos in culture

Balkan, Wayne; Rooman, Raoul; Hurst‐Evans, Amy; Phillips, Lawrence S.; Goldstein, Steven; Caju, M. V. L. Du; Sadler, T. W.

doi:10.1002/tera.1420380112

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…In this regard it has been shown that maternal dia betes or diabetes-like conditions alter the ultra structure and the function of the VYS [25]. Morphological changes in VYS are character ized by a decrease in vitelline vessel formation and in the number of cellular microvilli as well as by an increase in lysosomal-like structures and swollen mitochondria [26][27][28]. Function ally altered processing of protein and altered transfer of amino acids and peptides to the embryo have been related to an accumulation of serum protein in the VYS and to formation of giant lysosomes [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Glutathione Status in Diabetes-Induced Embryopathies

Menegola

Broccia²,

Ricolfi³

et al. 1996

Neonatology

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The mechanism involved in diabetes-induced embryotoxicity is still unclear. Mitochondrial alterations probably produced by oxidative stress have been described in embryos developing in a diabetic environment. Furthermore, oxygen radicals-scavenging enzymes can reduce the embryotoxic effects induced by diabetic conditions. In this work we tried to test if glutathione (GSH), a tripeptide implicated in cellular protection against reactive oxygen species, is involved in diabetes-related embryotoxicity. Rat embryos were explanted on day 11 on gestation from normal and from streptozotocin-diabetic mothers. The embryos were examined morphologically, then protein, DNA and GSH were determined both in embryos and in their visceral yolk sacs. The embryos explanted from diabetic mothers showed signs of developmental retardation and 16% were morphologically abnormal. GSH content was reduced in these embryos in comparison to control, but the GSH/protein in the visceral yolk sacs of conceptuses explanted from diabetic mothers was higher than in control visceral yolk sacs. Our hypothesis is that the reduction of embryonic GSH is a consequence of the alteration in GSH transport across the yolk sac endodermal cells damaged by diabetic conditions. The observed reduction in embryonic GSH could reduce the protection against the oxidative stress condition described in diabetic pathology.

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Section: Discussionmentioning

confidence: 99%

Glutathione Status in Diabetes-Induced Embryopathies

Menegola

Broccia²,

Ricolfi³

et al. 1996

Neonatology

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“…In the rat, high glucose concentrations were less teratogenic, at least in the strains tested [Sadler, 1980; Buchanan et al, 1985], leading to the postulate that additional serum factors contribute to teratogenesis [Sadler et al, 1988]: serum from insulin-treated diabetic rats was teratogenic despite normal glucose levels [Sadler and Horton, 1983], which was traced back to “somatomedin-inhibitors” [Balkan et al, 1988], now known as insulin-growth factor binding proteins.…”

Section: Maternal Diabetes and Neural Tube Defects In Animal Modelsmentioning

confidence: 99%

Modeling anterior development in mice: Diet as modulator of risk for neural tube defects

Kappen¹

2013

American J of Med Genetics Pt C

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Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient–gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity.

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“…Inhibitors with a similar molecular weight have been detected by other in¬ vestigators in normal urine and in uremic serum (24,25). Both our 1.2 kD fraction and the uremic inhib¬ itor produced abnormalities in mouse embryos (26). The structure of the 1.2 kD inhibitor and its mode of action is under investigation at present.…”

Section: Igf-i Binding Studiesmentioning

confidence: 90%

Isolation of several fractions from human serum, inhibiting rabbit cartilage metabolism in vitro

Rooman²

1990

Acta Endocrinologica

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In contrast to the well characterized serum stimulators of cartilage metabolism, information is scarce on the nature of circulating inhibitors. Human serum was fractionated by molecular sieving chromatography on Sephadex G-200, G-75, G-50 and Biogel P-4 gels. Six fractions with molecular weights of 150, 45, 30, 16, 9 and 1.2 kD inhibited [35S]sulphate incorporation into rabbit cartilage segments. All fractions but the smallest one exhibited their inhibitory effect only in the serum-stimulated cartilage. The 1.2 kD fraction impaired [35S]sulphate and [3H]methyl-thymidine incorporation into the cartilage segments in both stimulated and basal conditions. A seventh inhibitory fraction corresponded to the serum salt peak.The stimulatory effect of normal serum on the in vitro incorporation of sulphate and thymidine into cartilage from different animal species has been shown to be associated with the presence of somatomedins or insulin-like growth factors (1). Infor¬ mation on circulating inhibitors of cartilage metab¬ olism is scarce and their presence has been sug¬ gested in conditions of malnutrition (2,3), diabetes (4), and following insulin-induced hypoglycemia (5) and glucagon administration (6).The aim of this study was to investigate the pres¬ ence of inhibitory fractions in normal human serum. Several fractions with sulphation inhibitory activity are described.

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Somatomedin inhibitors from human serum produce abnormalities in mouse embryos in culture

Cited by 5 publications

References 30 publications

Glutathione Status in Diabetes-Induced Embryopathies

Glutathione Status in Diabetes-Induced Embryopathies

Modeling anterior development in mice: Diet as modulator of risk for neural tube defects

Isolation of several fractions from human serum, inhibiting rabbit cartilage metabolism in vitro

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