Chapter 69 - Developmental and reproductive disorders: role of endocrine disruptors in testicular toxicity

Abstract

This chapter describes how a variety of extraneous and internal factors can induce developmental and testicular toxicity leading to teratogenesis, poor sperm quality and male factor infertility. Developmental and reproductive toxicologists and epidemiologists have identified and classified several environmental chemicals and pharmaceutical products including teratogens and endocrine disruptors that lead to developmental and reproductive disorders. Hence, it is extremely important to understand the role of such toxicants and environmental endocrine disruptors. Convincing evidence exists that chemical exposures may lead to increased estrogenic activity, reduced androgen levels, or otherwise interfere with the action of androgen during development, thus causing male reproductive system abnormalities. The severity of testicular damage is related to the category of chemotherapeutic agent used, the dose and duration of therapy, and the developmental stage of the testis. The recovery of spermatogenesis is variable and depends upon the total therapeutic dose and duration of treatment. In addition to endocrine-disruptor mechanisms, endocrine disruptors including pesticides, xenobiotics, heavy metals, radiations, smoking and alcohol generate free radicals that can induce developmental and reproductive abnormalities. Reactive oxygen species (ROS) can also induce oxidation of critical-SH groups in proteins and DNA, which will alter cellular integrity and function with an increased susceptibility to attack by toxicants. The hazard identification and dose–response data are developed from experimental animal studies that may be supplemented with data from in vitro studies. This information is then extrapolated and integrated to characterize and assess the risk to the human population.