Critical windows of exposure for children's health: The reproductive system in animals and humans

Drugs and environmental chemicals can adversely affect the reproductive sys tem. Currently, available data indicate that the consequences of exposure d epend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. Th e reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundred s of millions of spermatozoa are generated daily by most adult male mammals , yet Very few of these germ cells succeed in transmitting their genetic ma terial to the next generation. Although the number of oocytes produced in m ammalian females is more limited, and their production occurs only during f etal life, most ovaries contain several orders of magnitude more oocytes th an ever will be fertilized. Toxicant exposures may affect critical events i n the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, externa l genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usua l animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach t o the identification of reproductive toxicants; and the development of sens itive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during e mbryonic, postnatal, and adult life.