Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 127, Issue 1-2, Pages 64-73Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2011.03.015
Keywords
Atrazine; Gonads; Endocrine disruptor
Funding
- TBH
- Novartis
- Syngenta Crop Protection
- Ecorisk
- National Science Foundation
- World Wildlife Fund
- Alton Jones Foundation
- Homeland Foundation
- Rose Foundation, Park-Water Company
- Biofaculty Award [UCB]
- Distinguished Mentor Award [UCB]
- Distinguished Teaching Award [UCB]
- Mitchell Kapor Foundation
- David Foundation
- Cornell-Douglas Foundation
- Wallace Global Fund
- Class of '43 Endowed Chair (UCB)
- Toxic Substances Research and Teaching Program (UCB), Hewlett Packard
- Howard Hughes Medical Institute
- McNair Scholars Program (UCB)
- Amgen Scholars Program (UCB)
- Mentored Research fellowship program (UCB)
- Center for Designing Foods to Improve Nutrition
- Dr. Scholl Foundation
- SRdS (Environment Canada)
- Ministry of the Environment, Japan
- National Institutes of Health
- National Science Funds, FNRS, Belgium
- Ministry of Science and Technology of the Republic of Croatia
- Ford Foundation
- Universidad Nacional del Litoral
- Argentine National Council for Science and Technology (CONICET)
- Argentine National Agency for the Promotion of Science and Technology
- National Institute of Environmental Health Sciences
- University of Florida Institute of Food and Agricultural Sciences
- CO & ABV-C (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq/Brazil
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES/Brazil
- Declining Amphibian Population Task Force and Depertment for Environmental, Food and Rural Affairs, UK
- Toxic Substances Research Initiative, Government of Canada
- Environment Canada
- Canadian Water Network
- Texas State University, San Marcos
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Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called Hill criteria (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause-effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects. Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis - demonstrated in fish, amphibians, reptiles, and mammals - represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus the case for atrazine as an endocrine disruptor that demasculinizes and feminizes male vertebrates meets all nine of the Hill criteria. (C) 2011 Published by Elsevier Ltd.
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