This proposal will investigate the physiological role of binding sites for platelet-activating factor (PAF), a glycerophospholipid, with potent smooth-muscle stimulating and vascular permeability inducing properties. It is hypothesized that PAF may be intimately involved in several events in the pre-implantation stage of pregnancy and in the preparation of the uterus for implantation.
The specific aims are to: 1) characterize the binding parameters of these PAF specific sites in rabbits, by comparing binding affinities and capacities of oviductal and uterine tissues in pregnant and pseudopregnant rabbits during the pre-implantation period, 2) determine how different hormonal conditions, e.g., estradiol and/or progesterone treatment affect these binding affinities and capacities in rabbits, 3) determine the presence of PAF binding sites on pre-implantation embryos, study their binding affinities and capacities in relation to embryonic growth and development, and determine their localization on the blastomeres in early stage embryos, and on the cells of the trophoblast and the inner cell mass at the blastocyst stage, 4) correlate changes in vascular permeability of the rabbit uterus with administration of synthetic PAF and the use of PAF inhibitors to block this response, 5) examine the relevance of embryoderived PAF for the ovum transport and implantation process by means of embryo transfer techniques following treatment of the embryos with synthetic PAF and PAF antagonists, 6) localize PAF binding sites in cells of rabbit and human uterine tissues, 7) determine whether dissociated human endometrial cell types (epithelial and stroma) display PAF binding similar to that measured in the rabbit, and examine the effect of steroid hormones on PAF binding in human epithelial and stromal cells in in vitro cultures. The research described above will enable us to determine in what manner PAF is involved in ovum transport and in the preparation of the uterus for implantation, and whether it is embryo-derived PAF or uterine-derived PAF which is responsible for the changes in vascular permeability that occur underlying the implanting blastocyst. Lastly, and most importantly, an initial determination will be able to be made as to whether the importance of PAF in the implantation process in the rabbit is species-specific or is of more general significance. This research will have important implications for elucidating factors operating in the pre-implantation period which may cause reduced fertility.
Showing the most recent 10 out of 11 publications
