Significance of incorporating measures of sperm production and function into rat toxicology studies

The rat is the preferred species for reproductive toxicity testing. The inc lusion of measures of rat sperm quality, such as motility and morphology, i nto reproductive test protocols often increases the sensitivity of the test to detect effects, and provides the toxicologist and risk assessor with va luable information about the nature of the reproductive toxicity of the tes t substance. Technical advances in computer-aided sperm analysis have made it possible to evaluate motion characteristics of rat spermatozoa. This tec hnology can provide an objective means of classifying the motion of rat spe rmatozoa as progressive or non-progressive, as required in test protocols. More specific tests of rat sperm function are being applied for the purpose of evaluating modes and mechanisms of toxicant action. Computer-aided sper m analysis can be used to evaluate sperm motion during cultures that suppor t sperm capacitation and to identify hyperactivated spermatozoa. Under the same culture conditions, acrosome-specific stains can be used to identify e ffects of toxicants on the acrosome reaction. These approaches, in combinat ion with in vitro fertilization in rats, can pinpoint sperm functional defi cits and thereby assist the toxicologist in addressing hypotheses regarding the cellular-molecular bases of toxicant-induced male infertility.