Endocrine disruption induced by triorganotin (IV) compounds: Impacts in the reproductive and genetic function

V. S. Delgado Filho¹, C. N. Mancini¹, I. V. Silva¹, D. F. Pedrosa^1,2, A. C. Destefani¹, V. Y. Samoto³, C. M. Takiya³ and J. B. Graceli¹*

¹Ageing Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Federal University of Espírito Santo, Vitória, ES, Brazil.

²Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória, ES, Brazil.

³Institute of Biomedical Sciences, Federal University of Rio de Janeiro, RJ, Brazil.

*Corresponding author. E-mail: jbgraceli@ccs.ufes.br, jbgraceli@gmail.com. 

Tel: +55-027-33357369. Fax: +55-27-33357358.

Accepted 9 June, 2010

 Abstract

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause irreversible sexual abnormality (masculinization) in female mollusks, called "imposex". However, it remains unclear whether organotin compounds also cause crucial toxicities in mammalian, including in human and rodents, in their sexual development and reproductive functions. Moreover, these compounds can act as potential competitive inhibitors of aromatase enzyme or others steroidogenic enzymes and recently, it was identified as agonists for retinoid X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR)γ, which are members of the nuclear receptor superfamily. Gene expression of human aromatase is regulated by the activation of PPARγ and/or RXR. In this review, the authors provide a discussion of the cellular, biochemical, and molecular mechanisms by which organotin compounds may cause adverse effects in the modulated genes involved in reproductive function.

Key words: Organotin, endocrine disruptor, aromatase, mammalian reproductive function.