Closer examination of the histopathological lesions that developed in the hamster uterus following neonatal DES exposure and later stimulation with E2 revealed that the hyperplastic endometrial epithelium also displayed intense apoptosis according to morphological (apoptotic bodies), biochemical (internucleosomal DNA fragmentation), and histochemical (in situ labeling of free 3′ DNA ends) evidence. According to Northern blot and immunohistochemical analyses, those neonatal DES-induced morphological responses in the uterus were accompanied by the altered expression of several proto-oncogenes that are implicated in the regulation of both cell proliferation (c-jun, c-fos, c-myc) and apoptosis (bax, bcl-2, bcl-x).
To provide a resource that would allow us to more fully define the phenomenon of neonatal DES-induced endocrine disruption throughout the female hamster reproductive tract and probe its mechanism at the cellular and molecular level, we have generated a comprehensive archive of formalin-fixed and paraffin-embedded tissues. This archive consists of various reproductive tract regions harvested at several time points from 1) prepubertal animals; 2) intact, mature animals; and 3) mature animals that were ovariectomized just before puberty and then exposed chronically to E2. other