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

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).

Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)

“…In addition to its persistence, mobility, and widespread contamination of water, atrazine is also a concern because several studies have shown that atrazine is a potent endocrine disruptor active in the ppb (parts per billion) range in fish (4, 5), amphibians (6)(7)(8)(9)(10)(11)(12), reptiles, and human cell lines (5,(13)(14)(15), and at higher doses (ppm) in reptiles (16)(17)(18), birds (19), and laboratory rodents (20)(21)(22)(23)(24)(25)(26)(27)(28). Atrazine seems to be most potent in amphibians, where it is active at levels as low as 0.1 ppb (6)(7)(8)(9)(10).…”

“…Atrazine seems to be most potent in amphibians, where it is active at levels as low as 0.1 ppb (6)(7)(8)(9)(10). Although a few studies suggest that atrazine has no effect on amphibians under certain laboratory conditions (29,30), in other studies, atrazine reduces testicular volume; reduces germ cell and Sertoli cell numbers (11); induces hermaphroditism (6,8,10); reduces testosterone (10); and induces testicular oogenesis (7)(8)(9)31). Furthermore, atrazine contamination is associated with demasculinization and feminization of amphibians in agricultural areas where atrazine is used (32) and directly correlated with atrazine contamination in the wild (7,9,33,34).…”

Remoção de atrazina e metabólitos pela filtração lenta com leito de areia e carvão ativado granular

“…Apesar dessas evidências existem escassos dados referentes àpresença destes no meio ambiente e seus efeitos na saúde (JIANG e ADAMS, 2006;HAYES et al, 2006;OH et al, 2003).…”

Molecular characterization and mRNA expression of ribosomal protein L8 in Rana nigromaculata during development and under exposure to hormones

“…Mostly, hey are used to evaluate reproductive endocrine disruption due to the high sensitivity of the reproductive system to sex hormones. Some EDCs have been demonstrated to induce the feminization of gonads and secondary sexual characteristics, transcription of estrogenic biomarkers, and sex hormone imbalance in amphibians (Hayes et al, 2006;Hogan et al, 2008;Qin et al, 2007). In addition, amphibians have become a unique biological model for studying thyroid-disrupting effects of EDCs because amphibian J O U R N A L O F E N V I R O N M E N T A L S C I E N C E S 2 6 ( 2 0 1 4 ) 2 3 3 1 -2 3 3 9 metamorphosis is controlled by thyroid hormone (TH) (Berg et al, 2009;Takase et al, 2007).…”

“…In the literature, Xenopus laevis is the most-used model amphibian species for endocrine disruption research (Degitz et al, 2005;Hayes et al, 2006). In addition, some native amphibian species, especially some species of the Rana genus, such as Rana catesbeiana (Veldhoen et al, 2006), Rana pipiens (Croteau et al, 2009), Rana temporaria (Mortensen et al, 2006) and Rana rugosa (Oka et al, 2009), have also been used as experimental species for assaying the endocrine-disrupting effects of chemicals.…”