Characterization of atrazine-induced gonadal malformations in African clawed frogs (Xenopus laevis) and comparisons with effects of an androgen antagonist (cyproterone acetate) and exogenous estrogen (17beta-estradiol): Support for the demasculinization/feminization hypothesis.

Atrazine is a potent endocrine disruptor that both chemically castrates and feminizes male amphibians. It depletes androgens in adult frogs and reduces androgen-dependent growth of the larynx in developing male larvae. It also disrupts normal gonadal development and feminizes the gonads of developing males. Gonadal malformations induced by atrazine include hermaphrodites and males with multiple testes [single sex polygonadism (SSP)], and effects occur at concentrations as low as 0.1 ppb (microg/L). Here, we describe the frequencies at which these malformations occur and compare them with morphologies induced by the estrogen, 17beta-estradiol (E2) , and the antiandrogen cyproterone acetate, as a first step in testing the hypothesis that the effects of atrazine are a combination of demasculinization and feminization. The various forms of hermaphroditism did not occur in controls. Nonpigmented ovaries, which occurred at relatively high frequencies in atrazine-treated larvae, were found in four individuals out of more than 400 controls examined (1%). Further, we show that several types of gonadal malformations (SSP and three forms of hermaphroditism) are produced by E2 exposure during gonadal differentiation, whereas a final morphology (nonpigmented ovaries) appears to be the result of chemical castration (disruption of androgen synthesis and/or activity) by atrazine. These experimental findings suggest that atrazine-induced gonadal malformations result from the depletion of androgens and production of estrogens, perhaps subsequent to the induction of aromatase by atrazine, a mechanism established in fish, amphibians, reptiles, and mammals (rodents and humans)

Characterization of atrazine-induced gonadal malformations in African clawed frogs (Xenopus laevis) and comparisons with effects of an androgen antagonist (cyproterone acetate) and exogenous estrogen (17beta-estradiol): Support for the demasculinization/feminization hypothesis.

Atrazine is a potent endocrine disruptor that both chemically castrates and feminizes male amphibians. It depletes androgens in adult frogs and reduces androgen-dependent growth of the larynx in developing male larvae. It also disrupts normal gonadal development and feminizes the gonads of developing males. Gonadal malformations induced by atrazine include hermaphrodites and males with multiple testes [single sex polygonadism (SSP)], and effects occur at concentrations as low as 0.1 ppb (microg/L). Here, we describe the frequencies at which these malformations occur and compare them with morphologies induced by the estrogen, 17beta-estradiol (E2) , and the antiandrogen cyproterone acetate, as a first step in testing the hypothesis that the effects of atrazine are a combination of demasculinization and feminization. The various forms of hermaphroditism did not occur in controls. Nonpigmented ovaries, which occurred at relatively high frequencies in atrazine-treated larvae, were found in four individuals out of more than 400 controls examined (1%). Further, we show that several types of gonadal malformations (SSP and three forms of hermaphroditism) are produced by E2 exposure during gonadal differentiation, whereas a final morphology (nonpigmented ovaries) appears to be the result of chemical castration (disruption of androgen synthesis and/or activity) by atrazine. These experimental findings suggest that atrazine-induced gonadal malformations result from the depletion of androgens and production of estrogens, perhaps subsequent to the induction of aromatase by atrazine, a mechanism established in fish, amphibians, reptiles, and mammals (rodents and humans)

Frequency of males, females, animals with SSP, and hermaphrodites in animals treated for s7, 14, or 49 days with 100 μg/L E

<p><b>Copyright information:</b></p><p>Taken from "Characterization of Atrazine-Induced Gonadal Malformations in African Clawed Frogs () and Comparisons with Effects of an Androgen Antagonist (Cyproterone Acetate) and Exogenous Estrogen (17β-Estradiol): Support for the Demasculinization/Feminization Hypothesis"</p><p></p><p>Environmental Health Perspectives 2006;114(S-1):134-141.</p><p>Published online 24 Jan 2006</p><p>PMCID:PMC1874169.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> -axis is categorical. Control bar shows the control sex ratio. NF stages below the bars indicate the stage at which E exposure was terminated. All E exposures began at NF stage 50 (). Numbers above bars are samples sizes and represent the number surviving to metamorphosis (of 90). Dashed line indicates 50%

SSP () and hermaphroditism () in animals treated for 7 days (NF stage 50–53) with 100 μg/L E

<p><b>Copyright information:</b></p><p>Taken from "Characterization of Atrazine-Induced Gonadal Malformations in African Clawed Frogs () and Comparisons with Effects of an Androgen Antagonist (Cyproterone Acetate) and Exogenous Estrogen (17β-Estradiol): Support for the Demasculinization/Feminization Hypothesis"</p><p></p><p>Environmental Health Perspectives 2006;114(S-1):134-141.</p><p>Published online 24 Jan 2006</p><p>PMCID:PMC1874169.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Six testes (three on each side) are numbered in . Abbreviations: O, ovary; T, testis. Scale bar = 0.1 mm for and

Gonads of a control postmetamorphic (NF stage 66) male (,) and female (,) African clawed frog ()

<p><b>Copyright information:</b></p><p>Taken from "Characterization of Atrazine-Induced Gonadal Malformations in African Clawed Frogs () and Comparisons with Effects of an Androgen Antagonist (Cyproterone Acetate) and Exogenous Estrogen (17β-Estradiol): Support for the Demasculinization/Feminization Hypothesis"</p><p></p><p>Environmental Health Perspectives 2006;114(S-1):134-141.</p><p>Published online 24 Jan 2006</p><p>PMCID:PMC1874169.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Abbreviations: OV, ovarian vesicle; K, kidney. (,) The entire kidney–interrenal–gonadal complex. The yellow color is the result of Bouin’s fixative. Arrowheads show the rostral and caudal ends of the animal’s right gonad. (,) Transverse cross-sections (8 μm) through the geometric center of each animal’s right gonad. Sections were stained with Mallory’s trichrome stain. Arrow indicates melanophore in the ovary. Scale bar: () 0.1 mm; () 10 μm. Figure adapted from

() Frequency of males, females, and specimens with gonadal malformations in controls and atrazine-treated animals (0

<p><b>Copyright information:</b></p><p>Taken from "Characterization of Atrazine-Induced Gonadal Malformations in African Clawed Frogs () and Comparisons with Effects of an Androgen Antagonist (Cyproterone Acetate) and Exogenous Estrogen (17β-Estradiol): Support for the Demasculinization/Feminization Hypothesis"</p><p></p><p>Environmental Health Perspectives 2006;114(S-1):134-141.</p><p>Published online 24 Jan 2006</p><p>PMCID:PMC1874169.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p>1–25 ppb). Numbers above bars are samples sizes and represent the number surviving to metamorphosis (of 90). Dashed line indicates 50%. () Frequency of gonadal malformations only. -axis is categorical