Efforts to clearly delineate the reproductive effects of exposures to man-made substances with estrogenic I properties have been hampered by the lack of suitable assay systems. The inadvertent exposure of mice in our colony to bisphenol A (BPA) during the course of meiotic studies provided evidence that this estrogen mimic disrupts mammalian female meiosis, causing specific meiotic phenotype at metaphase (congression failure) and an increased risk of nondisjunction at anaphase. Subsequent studies demonstrated that even short, low dose exposure produces a detectable meiotic effect, suggesting that the meiotic spindle provides a simple, reliable, and exquisitely sensitive assay system for the detection of reproductive toxins. The proposed studies will provide detailed dose-response information, assess the long-term impact of exposure on the genetic quality of eggs ovulated by sexually mature females, and begin to elucidate the molecular mechanisms underlying the meiotic disturbances. The potential impact of these studies is broad: The knowledge gained may be useful in developing a new assay for reproductive toxins and provide an important avenue for understanding the molecular mechanism of action of reproductive toxins. In addition, because the observed meiotic disruption (congression failure) is an age-related defect in human oocytes, the data may provide important insight to human age-related aneuploidy.
| Koehler, Kara E; Voigt, Robert C; Thomas, Sally et al. (2003) When disaster strikes: rethinking caging materials. Lab Anim (NY) 32:24-7 |
