Reproductive and developmental toxicity of endocrine-disrupting chemicals: steroid and nonsteroid mechanisms using rodent models

For toxicant-induced disruptions of endocrine mechanisms in wildlife populations, laboratory studies using well-defined rodent models can often serve as valuable adjuncts in the risk assessment process, especially since experimental databases for many wildlife species are not available. Because a variety of environmental toxicants have been reported to behave chemically as estrogens, androgens, or their receptor agonists or antagonists, much of the recent laboratory work on endocrine-disrupting chemicals (EDCs) has sought some resolution as to whether or not exposure to these agents could underlie many of the reproductive anomalies seen in the wild. During early rodent development, certain effects are consistent with steroid-like mechanisms of action, while other alterations suggest an interference with steroid signalling. In the adult female, a disruption in the hypothalamic control of pituitary function by acute exposures to a variety of nonsteroidal compounds can delay ovulation and apparently affect the development of any fertilized ova that may ensue. In many cases, what is becoming more evident is that environmental chemicals capable of influencing endocrine communication within the rodent reproductive system not only can affect the functional integrity of the exposed adult, but also can have a marked impact on early development. Since the association between reproductive dysfunction and chemical exposure in wildlife populations often involves some degree of reasoned speculation, such links can be strengthened when the detected alterations parallel those effects seen in the laboratory. Moreover, progressive refinements in both experimental testing paradigms and in our ability to assess exposures in the wild will increase the accuracy with which the endocrine-disruptive alterations in reproductive success can be identified and eventually predicted.