Aging and responses to toxins in female reproductive functions

Reproductive senescence in laboratory rodents has been well characterized using vaginal smear analysis, a relatively simple and inexpensive technique to monitor changes in estrous cyclicity. Although some differences exist, laboratory animal models are available to study most aspects of age-related changes in human reproductive physiology (4,13). Thus presumptive reproductive toxins can be tested on laboratory rodents using the qualitative and quantitative parameters for estrous cyclicity described here to assess damage. Before implementing such tests, however, certain limitations must be considered. Quantitative changes in estrous cycles, for example, cycle length distribution, which indicate more subtle impairments in reproductive function, require more refined data analysis. In particular, baseline data for at least one month is required before exposure to the presumptive toxin. In addition, the period of maximum cycling regularity is fairly short (three to four months duration) so long-term exposures to presumptive toxins would not be applicable. Longer term exposure (greater than or equal to six months) would be permissible if qualitative changes in cyclicity (i.e., acyclic vs. cyclic) were the dependent variable used to assess toxicity. Finally, if other parameters of reproductive function (e.g., fertility, litter size) are used to assess reproductive toxicity, we urge that cycling characteristics of the offspring be carefully monitored to assess possible cryptic damage to later neuroendocrine functions that occurred to the fetuses in utero.