RECEPTIVITY IS A POLARITY DEPENDENT SPECIAL FUNCTION OF HORMONALLY REGULATED UTERINE EPITHELIAL-CELLS

Useful knowledge of the mechanisms which regulate ovoreceptivity and implantation remains elusive in spite of increasing efforts to apply the technology of biochemistry and to a lesser extent, cellular and molecular biology to the analysis of the problem. Existing models used to analyze interactions of the blastocyst and endometrial cells of the uterus have been unable to account for nongenotypic embryonic losses, particularly those following in vitro fertilization and embryo transfer. Separation of endometrial uterine epithelial (UE) and uterine stromal (US) cells was used to demonstrate that each cell type responds independently and interdependently to the same regulatory signals. Cultured by classical techniques UE cells proved unable to respond to steroid hormone signals. For this reason UE cell cultures could not be used to develop an experimental cell system that mimicked growth and development of UE cells in utero. The failure of classical UE cell cultures derived from their inability to maintain epithelial cell polarity. Polarity, the spatial asymmetry of plasma membrane domains, is intrinsic to the structure and function of an epithelial cell. Apical and basolateral surfaces have different lipid and protein compositions which are correlates of the special functions of that epithelial cell. As epithelial cells differentiate they must, in response to regulatory cues, direct the flux of membrane components moving into and out of each surface in order to establish the polarity characteristic of each stage specific expression. The acquisition of receptivity by the apical surface of the UE cell may be considered to be such a special function. To prove this hypothesis polarized cultures of primary UE cells had to be developed that were hormonally responsive. Such an experimental cell system could serve as a model for in vitro implantation. This essay describes such a culture system in which blastocysts cocultured with UE cells in the presence of estrogen, will as predicted, fail to attach. This polarized UE cell system provides a functional in vitro model to study ovoreceptivity. It is now feasible to initiate studies of hormonal regulation of the composition and function of UE cell plasma membranes as they reflect the nonreceptive, receptive, and refractory nature of its apical surface.