Expression of insulin, insulin-like growth factor I and glucocorticoid receptor in rat uterus and embryo during decidualization, implantation and organogenesis

Abstract

The significance of insulin, insulin-like growth factor I (IGF-I) and glucocorticoids to the early mammalian embryo is clear in that they are key regulators of both mitogenic and metabolic effects during development. In the present study, the temporal sequence of expression of the respective receptor proteins was investigated for the first time in the developing rat utero-embryonic unit between conception and day 12 of gestation using immunocytochemistry. Insulin, IGF-I and glucocorticoid receptor were expressed in embryonic tissues after the start of implantation, and were co-localized in the primary ectoderm, extraembryonic ectoderm as well as in the ectoplacental cone. The parietal endoderm was devoid of glucocorticoid receptor staining, whereas IGF-I receptor was absent in visceral endoderm. After completion of basic organogenesis, the neural tube, notochord, otic placode, Wolffian duct, mesonephros and intestinal tube expressed insulin, IGF-I and glucocorticoid receptor. The glucocorticoid receptor was not expressed in heart tube and dorsal aortae. Considerable amounts of insulin receptor were detected in trophoblast-derived giant cells. In the uterus, luminal epithelium, endometrial stromal and myometrial smooth muscle cells immunoreacted with antisera against insulin, IGF-I and glucocorticoid receptor. Endometrial glands remained negative for the glucocorticoid receptor throughout the gestational period investigated. Uterine hormone receptor expression reached a peak at days 4 and 5 of gestation in endometrial stromal cells and decidua, respectively. In conclusion, the demonstrated ontogenetic pattern of insulin, IGF-I and glucocorticoid receptor expression indicates the potential sites of biological action of the respective ligands, providing supportive evidence for their critical importance during the course of embryogenesis in rats.