| 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 (17β-Estradiol): Support for the Demasculinization/Feminization Hypothesis Tyrone B. Hayes, A. Ali Stuart, Magdalena Mendoza, Atif Collins, Nigel Noriega, Aaron Vonk, Gwynne Johnston, Roger Liu, and Dzifa Kpodzo Laboratory for Integrative Studies in Amphibian Biology, Group in Endocrinology, Museum of Vertebrate Zoology, Energy and Resources Group, and Department of Integrative Biology, University of California, Berkeley, California, USA Abstract
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 (µg/L) . Here, we describe the frequencies at which these malformations occur and compare them with morphologies induced by the estrogen, 17β-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) . Key words: amphibians, atrazine, chemical castration, endocrine disruption, feminization, hermaphroditism. Environ Health Perspect 114(suppl 1) :134-141 (2006) . doi:10.1289/ehp.8067 available via http://dx.doi.org/ [Online 24 January 2006]
This article is part of the monograph "The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife." Address correspondence to T.B. Hayes, Laboratory for Integrative Studies in Amphibian Biology, Department of Integrative Biology, University of California, Berkeley, CA 94720-3140 USA. Telephone: (510) 643-1054. Fax: (510) 643-6264. E-mail: tyrone@berkeley.edu We thank Novartis, Syngenta Crop Protection, Ecorisk Inc., and members of the Atrazine Endocrine Ecological Risk Assessment Panel of Ecorisk Inc. for comments, criticisms, and encouragement. All work was conducted in compliance with animal use protocol R209-0402BCR to T.B.H. We thank H.H. Wheeler and Park Water Company for funding parts of the work. This work was also funded by a grant from the National Science Foundation (IBN-9513362) and by the Biology Faculty Award, University of California-Berkeley to T.B.H. N.N. was a Presidential Fellow (University of California, Berkeley) when the work was conducted. D.K., R.L., and G.J. were funded by the Howard Hughes Biology Scholar's Program. The authors declare they have no competing financial interests. Received 31 January 2005 ; accepted 23 January 2006.
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