Effects of estrogenic hormones on early development ofXenopus laevis

The exposure of Bufo arenarum embryos to 25 µmol/L 17β-estradiol (E 2 ) resulted in 100% lethality within 48 hr, whereas 10 µmol//L E 2 was the no observed effect concentration value for shortterm chronic (7 days) exposure. The toxicity profile curves show that lethal effects were proportional to the E 2 concentration and the time of exposure. The E 2 uptake resulted in 20.1 ng E 2 /mg embryo at 8 hr posttreatment, but 67.3% of this value was achieved during the first 30 min of incubation with this estrogen. Regarding metabolism, the embryos synthesize estrone (E 1 ) from E 2 by means of 17β-hydroxysteroid dehydrogenase. Simultaneous treatments of Bufo arenarum embryos with 1 mg/L Cd 2+ and 0.1, 1, or 10 µmol/L E 2 enhanced the lethality exerted by cadmium in 76.7, 80, and 83.3% of embryos, respectively. The results indicate that estrogenic endocrine disruptors could have an adverse effect on amphibian embryos and enhance the toxic effect of Cd on amphibian embryos. This study points to the possibility of using the AMPHITOX test as a screening method for potential endocrine disruption as well as the combined effects of chemical mixtures.

Section: Discussionmentioning

confidence: 99%

Estradiol uptake, toxicity, metabolism, and adverse effects on cadmium-treated amphibian embryos.

Fridman

Corró

Herkovits

2004

“…The effects reported for exposure to this synthetic compound mirror those produced by the naturally occurring estrogen 17β estradiol) (E 2 ) (Nishimura et al 1997), which is consistent with a common mechanism of action for NPEO and E 2 . Specifically, Nishimura et al (1997) demonstrated that exposure (beginning at stage 3) to 10 µM E 2 caused increases in mortality and increased incidence of malformations, including crooked vertebrae, swollen stomachs, small eyes and heads, and suppressed organogenesis of digestive organs and the nervous system.…”

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confidence: 99%

“…Specifically, Nishimura et al (1997) demonstrated that exposure (beginning at stage 3) to 10 µM E 2 caused increases in mortality and increased incidence of malformations, including crooked vertebrae, swollen stomachs, small eyes and heads, and suppressed organogenesis of digestive organs and the nervous system. In this study no deleterious effects of E 2 exposure were evident before stage 27, but subsequent to this developmental stage both the incidence of malformations and mortality increased, and all embryos died by stage 42.…”

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confidence: 99%

Environmental estrogens alter early development in Xenopus laevis.

Bevan

Porter

Prasad

et al. 2003

A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. We exposed Xenopus laevis embryos at early gastrula to the commonly encountered environmental estrogens nonylphenol, octylphenol, and methoxychlor, the antiandrogen, p,p-DDE, or the synthetic androgen, 17 alpha-methyltestosterone at concentrations ranging from 10 nM to 10 microM and examined them at tailbud stages (approximately 48 hr of treatment). Exposure to the three environmental estrogens, as well as to the natural estrogen 17 beta-estradiol, increased mortality, induced morphologic deformations, increased apoptosis, and altered the deposition and differentiation of neural crest-derived melanocytes in tailbud stage embryos. Although neural crest-derived melanocytes were markedly altered in embryos treated with estrogenic toxicants, expression of the early neural crest maker Xslug, a factor that regulates both the induction and subsequent migration of neural crest cells, was not affected, suggesting that the disruption induced by these compounds with respect to melanocyte development may occur at later stages of their differentiation. Co-incubation of embryos with the pure antiestrogen ICI 182,780 blocked the ability of nonylphenol to induce abnormalities in body shape and in melanocyte differentiation but did not block the effects of methoxychlor. Our data indicate not only that acute exposure to these environmental estrogens induces deleterious effects on early vertebrate development but also that different environmental estrogens may alter the fate of a specific cell type via different mechanisms. Finally, our data suggest that the differentiation of neural crest-derived melanocytes may be particularly sensitive to the disruptive actions of these ubiquitous chemical contaminants.

“…These authors also found that sex ratios favored males in juvenile A. crepitans collected from sites contaminated by polychlorinated biphenyls and polychlorinated dibenzofurans. Nishimura et al (19) raised X. laevis in water containing different concentrations of E 2 and observed malformations of the head and abdomen, suppressed organogenesis, and suppressed nervous system development at 10 -5 M. Although the dose Nishimura et al (19) used exceeds physiologic levels, the findings suggest that estrogen exposure can disrupt brain development. Accelerated metamorphosis was observed after the treatment of Bufo bufo and B. americanus tadpoles with E 2 (20) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (21).…”

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confidence: 99%

Octylphenol and UV-B radiation alter larval development and hypothalamic gene expression in the leopard frog (Rana pipiens).

Crump

Lean

Trudeau

2002

We assessed octylphenol (OP), an estrogenic endocrine-disrupting chemical, and UV-B radiation, a known stressor in amphibian development, for their effects on hypothalamic gene expression and premetamorphic development in the leopard frog Rana pipiens. Newly hatched tadpoles were exposed for 10 days to OP alone at two different dose levels; to subambient UV-B radiation alone; and to two combinations of OP and UV-B. Control animals were exposed to ethanol vehicle (0.01%) exposure, a subset of tadpoles from each treatment group was raised to metamorphosis to assess differences in body weight and time required for hindlimb emergence. Tadpoles from one of the OP/UV-B combination groups had greater body weight and earlier hindlimb emergence (p < 0.05), but neither OP nor UV-B alone produced significant changes in body weight or hindlimb emergence, indicating a potential mechanism of interaction between OP and UV-B. We hypothesized that the developing hypothalamus might be a potential environmental sensor for neurotoxicologic studies because of its role in the endocrine control of metamorphosis. We used a differential display strategy to identify candidate genes differentially expressed in the hypothalamic region of the exposed tadpoles. Homology cloning was performed to obtain R. pipiens glutamate decarboxylases--GAD65 and GAD67, enzymes involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). cDNA expression profiles revealed that OP and UV-B affected the levels of several candidate transcripts in tadpole (i.e., Nck, Ash, and phospholipase C gamma-binding protein 4 and brain angiogenesis inhibitor-3) and metamorph (i.e., GAD67, cytochrome C oxidase, and brain angiogenesis inhibitor-2 and -3) brains. This study represents a novel approach in toxicology that combines physiologic and molecular end points and indicates that levels of OP commonly found in the environment and subambient levels of UV-B alter the expression of important hypothalamic genes and disrupt tadpole growth patterns.