Interactive effects of cadmium and retinoic acid on mouse limb bud development in vitro

Shury, Todd; Rousseaux, Colin G.; Keiner, Judy; Politis, Michael J.

doi:10.1007/bf00199028

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…For example, CdCl 2 did not enhance RA‐induced hindlimb duplication or neural tube defects when coadministered at other time points (unpublished data, X. Liao). No significant interactions between cadmium and RA were found by other researchers when using mouse limb bud culture or rat pituitary cell culture (Shury et al,1994; Mostbock et al,2002). Cadmium has been shown to have potent estrogen‐ and androgen‐like activities in vivo and in vitro by directly binding to estrogen and androgen receptors, which are zinc finger nuclear hormone receptors (Stoica et al,2000; Martin et al,2002; Takiguchi and Yoshihara,2006).…”

Section: Discussionmentioning

confidence: 75%

Genetic and pathologic aspects of retinoic acid‐induced limb malformations in the mouse

Lee

Liao

Shimizu

et al. 2010

Birth Defects Research

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Because all-trans retinoic acid (atRA) is teratogenic in all species tested and many of the specific defects induced are common across the phylogenetic spectrum, it would be logical to predict that murine strain differences in teratology to this agent are minimal. However, for specific defects, strain susceptibilities are vastly different. Studies with atRA have shown stark differences between C57BL/6 and SWV mouse strains in susceptibility to postaxial forelimb ectrodactyly and ectopic hindlimb formation, with the C57 strain being more susceptible for both defects. Various approaches were used to determine why these strains differ in susceptibility, but the mechanisms remain unknown. Hindlimb duplications were hypothesized to be caused by the formation of ectopic posterior body axes. For forelimb ectrodactyly, a locus on chromosome 11, Rafar, has linkage to the strain difference, and mRNA localization has shown that specific genes (Fgf8, Dlx3, Bmp4, and Sp8) in the postaxial preAER (prior to formation of the apical ectodermal ridge) of the developing limb bud (the site of the defect) were downregulated hours after atRA administration more in the susceptible C57 than in the SWV strain. Because both atRA and divalent cadmium induce postaxial forelimb ectrodactyly (right-sided predominance) at a high rate in C57BL/6 and low in the SWV strain, there is debate as to whether they share a common mechanism. These teratogens cause a greater-than-additive level of forelimb ectrodactyly when coadministered at low doses, but cadmium does not induce ectopic hindlimb formation. The hypothesis is that these agents have separate molecular pathologic pathways that converge to perturb a common anatomic structure.

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Section: Discussionmentioning

confidence: 75%

Genetic and pathologic aspects of retinoic acid‐induced limb malformations in the mouse

Lee

Liao

Shimizu

et al. 2010

Birth Defects Research

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“…and in parallel with the expression of TH receptors (for a recent review of TH induced metamorphosis, see Furlow and Neff [29]). Cadmium, a well‐known teratogen of mammals [30], has been shown to interact with retinoic acid, altering limb development in mice [31]. Few studies have been directed at the interactions of RXR and heavy metals.…”

Section: Discussionmentioning

confidence: 99%

Critical period of sensitivity for effects of cadmium on frog growth and development

Gross

Johnson

Prahl

et al. 2009

Enviro Toxic and Chemistry

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Cadmium is a ubiquitous pollutant in aquatic environments that can alter organismal physiology and ecology. Previous experiments found that ecological Cd exposures increased the growth and development of two North American anurans. However, the generality of these effects among species, the time period over which they occur, and the mechanisms responsible remain conjectural. The goal of the present study was to determine the critical period of sensitivity of Rana pipiens exposed to ecologically relevant levels of Cd. We exposed tadpoles to Cd (0 [control], 1.0, and 10.0 microg/L) from Gosner stage (GS) 25 to metamorphic climax. We assessed effects of Cd on amphibian length, survival, and development during premetamorphosis (GS 25-30) and prometamorphosis (GS 31-42). After 14 d of exposure, we staged tadpoles and recorded snout-vent length. Tadpoles were then pooled according to treatment and stage (GS < or =29 or GS > or =30) and allowed to undergo metamorphic development. Tadpoles exposed to 10 microg/L were significantly larger and more advanced in development by 14 d. Survival to forelimb emergence exceeded 90% in all treatments, and time to metamorphic climax was not different from that in controls. Body burdens of Cd were positively correlated with increasing treatment. Early amphibian development (premetamorphosis) was shown to be the critical period of sensitivity for growth and development. Whereas the freshwater criterion for Cd appears to be protective for survival, a lack of knowledge remains about the sublethal effects of chronic exposures of metal pollutants, especially as they relate to tissue concentrations at various stages of amphibian life history.

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“…To date, the interactive effects between cadmium and RA have not been examined in teratology studies, except for a single in vitro study. The in vitro study investigated the dysmorphogenic effects of CdCl 2 and RA in a murine limb bud culture system (Shury et al,1994). The authors of that study concluded that there was an antagonistic effect between CdCl 2 and RA in limb bud culture, but the data did not unequivocally support that conclusion.…”

Section: Discussionmentioning

confidence: 99%

Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice

et al. 2006

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Interactive effects of cadmium and retinoic acid on mouse limb bud development in vitro

Cited by 5 publications

References 12 publications

Genetic and pathologic aspects of retinoic acid‐induced limb malformations in the mouse

Genetic and pathologic aspects of retinoic acid‐induced limb malformations in the mouse

Critical period of sensitivity for effects of cadmium on frog growth and development

Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice

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