Induction of Skeletal Malformations in the Offspring of Rats Fed a Zinc Deficient Diet

Styrud, Johan; Dahlström, V. Elisabeth; Eriksson, Ulf J.

doi:10.3109/03009738609178488

Cited by 19 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of zinc in the skeleton, which contains the major portion of total body zinc, is not clear [30]. However, resulting skeletal malformation in the offspring whose dams were fed a Zn-restricted diet during pregnancy is well known [31,32]. Skeletal growth impairment is a common finding associated with zinc deficiency [33].…”

Section: Discussionmentioning

confidence: 99%

Effects of Caffeine on the Bones of Aged, Ovariectomized Rats

et al. 1999

View full text Add to dashboard Cite

Caffeine is a substance which many people consume in their daily life. Caffeine’s effects on bone are still controversial. Using ovariectomized rats, the present study was conducted to determine to what extent caffeine intake affects the mechanical properties, bone minerals and histology. Aged rats were divided into 2 groups after ovariectomy. Group 1 was fed a 20% protein diet as a control, and group 2 was fed a 20% protein diet supplemented with caffeine (2 mg/100 g body weight). The respective diets were fed to the rats of each group for 90 days. Rats were then killed by heart puncture, blood was collected, and femurs were removed. In 1 group of femurs paraffin cross-sections were made at the midshaft of each bone. Total width, cortical width, total cross-sectional bone area of the midshaft, and the number of osteocytes in randomly selected areas were measured. Another group of bones was subjected to three-point bending testing until failure. Bones were then pulverized and Ca, P, Mg, Zn, Sr, Si, hydroxyproline and hexosamine contents and crystallite size were measured. Various mechanical properties, except modulus of elasticity, in the caffeine group were consistently 7–23% lower than the noncaffeine controls. Yield strain in the caffeine group was significantly less than in the noncaffeine controls. Zinc, Sr, and crystallite size of bone showed a significant decrease in the caffeine group, whereas Si contents significantly increased. Our current results indicate that routine intake of caffeine in the elderly should be regarded with some caution.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Caffeine on the Bones of Aged, Ovariectomized Rats

et al. 1999

View full text Add to dashboard Cite

show abstract

“…We have previously demonstrated that normal pregnant U rats on a zinc-deficient diet are more prone to have fetal skeletal malformations than H rats given the same diet (54). A leakage of albumin via the kidneys may predispose for trace metal shortage, because albumin serves as carrier and plasma reservoir for several of these, including zinc.…”

Section: Ud Hn Hdmentioning

confidence: 99%

Correlations between Maternal Metabolism and Deranged Development in the Offspring of Normal and Diabetic Rats

et al. 1995

Self Cite

View full text Add to dashboard Cite

In an attempt to define the pathogenesis of congenital malformations in diabetic pregnancy, a number of serum factors were determined in normal and diabetic pregnant rats and correlated to the outcome of gestation with the aid of multivariate linear regression analysis. The animals were from two different lines of Sprague-Dawley rats with documented differences in rates of fetal dysmorphogenesis in diabetic pregnancy. The diabetic rats increased less in body weight than the normal rats, yet displayed increased liver and kidney weights. The serum concentrations of glucose, P-hydroxybutyrate, triglycerides, the branched-chain amino acids, and asparagine, proline, alanine, citrulline, tyrosine, and ornithine were increased by diabetes. In contrast, IGF-I, glutamic acid, glutamine, cystine, and lysine were decreased in the serum of the diabetic pregnant rats. The maternal metabolic imbalance exerted profound effects on embryonic development. Thus, the embryos of the diabetic rats were smaller, had fewer somites, and contained less DNA and protein than the control embryos. In addition, the resorption and malformation rates were increased in the embryos of the diabetic rats. The regression analysis of the data revealed significant interrelationships between adverse embryonic outcome (rates of malformations and resorptions) and the maternal serum concentrations of glucose, triglycerides, P-hydroxybutyrate, branched-I---Diabetic pregnancy is associated with an increased risk of fetal maldevelopment (1-3). The pathogenesis of congenital malformations in the offspring of diabetic mothers is unknown. In previous clinical and experimental studies, strict metabolic control of the mother has been shown to diminish the risk of fetal maldevelopment, especially if the improved control is initiated in early pregnancy (4-7) or before conception (8).chain amino acids, and creatinine. This suggests that the maternal metabolism of the three major classes of nutrients covariates with the embryonic development in diabetic rat pregnancy. The monitoring of only one of these maternal parameters, e.g. the serum glucose concentration, may therefore not adequately predict the developmental status of the offspring. Our results suggest that the pathogenesis of fetal malformations in diabetic pregnancy is multifactorial. Thus, maintaining metabolites from all nutrient classes at a normal level may be important in preventing adverse fetal outcome. Maintenance of normal serum glucose levels alone, however, does not seem to completely protect the fetus from malformations (9). Other disturbed metabolic processes in the mother, reflected by alterations in serum levels of associated metabolites, may therefore have pathogenic roles in the teratogenicity of diabetic pregnancy. In previous studies of an animal model for diabetic pregnancy, w e found increased rates of fetal malformations and resorptions among the offspring of streptozotocin-diabetic rats

show abstract

“…The last week of gestation is considered to be a ''catabolic phase'' in which maternal nutritional stores are consumed to support the rapidly growing fetus. Deficiencies of specific nutrients, such as zinc, also can lead to delayed ossification (Styrud et al, 1986).…”

Section: Determinants Of Ossification Ratementioning

confidence: 99%

Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs

Carney

Kimmel²

2007

Birth Defects Research Pt B

View full text Add to dashboard Cite

Delayed (or incomplete) ossification of developing fetal bones and wavy ribs are some of the most common skeletal variations encountered in regulatory guideline developmental toxicity studies. Although they tend to be regarded as minor effects, they can be quite sensitive and consequently may influence the study lowest-observed-adverse-effect levels (LOAELs), and thus, impact classification, labeling, and risk assessment. In this study, we review the underlying mechanisms of these skeletal variations, evaluate different scenarios in which they have been observed, offer guidance for their interpretation, and comment on their use for risk assessment. Both minor delays in ossification and wavy ribs seem to be readily repairable via postnatal skeletal remodeling, are not mechanistically linked to malformation, and often are seen in the presence of maternal or fetal toxicity. As such, these minor variations would not generally be considered adverse in and of themselves but should be interpreted in the context of other maternal and fetal findings, information available on normal skeletogenesis patterns, mode of action of the test agent, and historical control incidence using a weight of evidence approach. Birth Defects Res 80: 473-496, 2007. r 2007

show abstract

Induction of Skeletal Malformations in the Offspring of Rats Fed a Zinc Deficient Diet

Cited by 19 publications

References 20 publications

Effects of Caffeine on the Bones of Aged, Ovariectomized Rats

Effects of Caffeine on the Bones of Aged, Ovariectomized Rats

Correlations between Maternal Metabolism and Deranged Development in the Offspring of Normal and Diabetic Rats

Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs

Contact Info

Product

Resources

About