Reproductive toxins: Pervasive theme of oxidative stress and electron transfer

Reproductive toxicity has been a topic of increasing interest and concern in recent years, generating- controversy in association with danger to humans and other living things. A veritable host of chemicals is known to be involved, encompassing a wide variety of classes, both organic and inorganic. Exposure is pervasive and virtually unavoidable due to contamination of air, water, ground, food, beverages, drugs, and household items. The corresponding adverse effects on reproduction are numerous. There is uncertainty regarding mode of action although various theories have been advanced, e.g., disruption of the CNS, DNA attack, enzyme inhibition, interference with hormonal action, and insult to membranes and proteins. This review provides extensive evidence for involvement of oxidative stress (OS) and electron transfer (ET) as a unifying theme. Successful application is made to all of the main classes of toxins, in addition to large numbers of miscellaneous types. We believe it is not coincidental that the vast majority of these substances incorporate ET functionalities (quinone, metal complex, ArNO2, or conjugated iminium) either per se or in metabolites, potentially giving rise to reactive oxygen species (ROS) by redox cycling. Some categories, e.g., peroxides and radiation, appear to generate ROS by non-ET routes. For completeness, other theories are also addressed; a multifaceted approach appears to be the most logical. Our framework should increase understanding and contribute to preventative measures, such as use of antioxidants (AOs). The ET-OS theory has recently been used as the central theme by us in reviews of biomechanisms involved with anti-infective drugs, anticancer agents, and carcinogens (see text).