Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 32, Issue 5, Pages 290-299Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2011.01.001
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Funding
- National Institutes of Health [NICHD U54 HD029990, R01 HD056034, R01 HD056034-02S1]
- University of Hong Kong (Hong Kong, China)
- Noopolis Foundation (Rome, Italy)
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Male infertility caused by exposure to environmental toxicants such as cadmium, mercury, bisphenol A (BPA) and dioxin is a global problem, particularly in industrialized countries. Studies in the testis and other organs have illustrated the importance of environmental toxicant-induced oxidative stress in mediating disruption to cell junctions. This, in turn, is regulated by the activation of PI3K/c-Src/FAK and MAPK signaling pathways, with the involvement of polarity proteins. This leads to reproductive dysfunction such as reduced sperm count and reduced quality of semen. In this review, we discuss how these findings can improve understanding of the modes of action of environmental toxicants in testicular dysfunction. Thus, specific inhibitors and/or antagonists against signaling molecules in these pathways may be able to 'reverse' and/or 'block' the disruptive effects of toxicant-induced damage. Additional studies comparing high-level acute exposure versus low-level chronic exposure to environmental toxicants are also needed to fully elucidate the underlying molecular mechanism(s) by which these toxicants disrupt male reproductive function.
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