title: 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.
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 (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).
authors.affiliation: Laboratory for Integrative Studies in Amphibian Biology, Group in Endocrinology, Museum of Vertebrate Zoology, Department of Integrative Biology, University of California, Berkeley, California 94720-3140, USA. tyrone@berkeley.edu
authors.forename: Tyrone B
authors.initials: TB
authors.lastname: Hayes
authors.forename: A Ali
authors.initials: AA
authors.lastname: Stuart
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mendoza
authors.forename: Atif
authors.initials: A
authors.lastname: Collins
authors.forename: Nigel
authors.initials: N
authors.lastname: Noriega
authors.forename: Aaron
authors.initials: A
authors.lastname: Vonk
authors.forename: Gwynne
authors.initials: G
authors.lastname: Johnston
authors.forename: Roger
authors.initials: R
authors.lastname: Liu
authors.forename: Dzifa
authors.initials: D
authors.lastname: Kpodzo
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D003430:Cross-Sectional Studies; D017373:Cyproterone Acetate / Q000494:pharmacology*; D012734:Disorders of Sex Development / Q000139:chemically induced / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005262:Feminization / Q000139:chemically induced* / Q000453:epidemiology; D006066:Gonads / Q000002:abnormalities* / Q000187:drug effects; D008297:Male; D008675:Metamorphosis, Biological / Q000187:drug effects; D008954:Models, Biological; D012733:Sex Differentiation / Q000187:drug effects / Q000502:physiology; D014982:Xenopus laevis / Q000002:abnormalities*
chemical_list: D000726:Androgen Antagonists; D017373:Cyproterone Acetate; D004958:Estradiol; D001280:Atrazine