Disclaimer. The research described in this presentation has been reviewed by the National Health Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals†
Article first published online: 7 FEB 2006
International Journal of Andrology
Volume 29, Issue 1, pages 96–104, February 2006
How to Cite
Earl Gray, L., Wilson, V. S., Stoker, T., Lambright, C., Furr, J., Noriega, N., Howdeshell, K., Ankley, G. T. and Guillette, L. (2006), Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. International Journal of Andrology, 29: 96–104. doi: 10.1111/j.1365-2605.2005.00636.x
- Issue published online: 7 FEB 2006
- Article first published online: 7 FEB 2006
- Received 30 May 2005; revised 14 September 2005; accepted 15 September 2005
- CAFO feedlot effluent;
- p,p′DDT and p,p′DDE;
- polybrominated diphenyl ethers;
- pulp mill effluent;
- sexual differentiation;
Within the last decade, several classes of chemicals have been shown in laboratory studies to disrupt reproductive development by acting as androgen receptor (AR) antagonists and/or inhibitors of fetal Leydig cell testosterone production. Some phthalate esters alter gubernacular differentiation by reducing insulin-like 3 (insl3) mRNA levels. We have found that AR antagonists and inhibitors of fetal testis hormone production generally induce cumulative, apparently dose-additive adverse effects when administered in mixtures. New research has also revealed the presence of androgens in the environment. Effluents from pulp and paper mills display androgenic activity of sufficient potency to masculinize and/or sex-reverse female fish. Effluent from beef cattle concentrated animal feedlot operations from the United States also displays androgenic activity in vitro, due, in part, to the presence of a steroid used to promote growth in beef cattle. In summary, we are only beginning to identify the classes of chemicals that have the potential to alter the androgen signalling pathway in utero. This review will (i) present information on the classes of environmental chemicals that display antiandrogenic and androgenic activities in vitro and in vivo, and (ii) provide an insight into how exposure to mixtures these chemicals might behave in utero.