DIFFERENTIAL TROPHOBLAST FORMATION FROM RHESUS EMBRYONIC STEM CELLS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To investigate the endometrial immunomorphological response to procedures mimicking embryo transfer (MET) in rhesus monkey. PROGRESS: Although substantial progress was made in IVF technology in recent decades, the implantation rate remains low. Because it is not possible to conduct direct investigation of embryo invasion in early human pregnancy, the morphophysiological similarity of the reproductive tract makes the rhesus monkey a valuable animal model for the in vivo study of the interactions between the human embryo and endometrium during the implantation process. The study consisted of four animal groups: 1) One animal with tubal and two animals with transcervical MET, using rhesus ES cell-derived embryoid bodies (EB transfer); 2) Two animals with transcervical MET with EB-media only (Sham transfer); 3) Two animals treated with progesterone without MET; and 4) One animal as an untreated control. Animals were euthanized on day 9 or 10 (one monkey on day 21) post transfer. We conducted immunohistochemistry for leukocyte subset and endothelial markers and PAS-staining with vascular and general endometrial morphometry. Immunostaining revealed a decreased number of NK cells (CD56+ and perforin+), CD68+ macrophages and neutrophils in upper layer of endometrium in all experimental groups compared with the untreated control. These changes in leukocyte subsets coincide with decreases in the stromal cell density, increases in the endometrial thickness and vascularity. In the basal endometrium, the number of perforin+ cells increased in all animals, while T cells decreased in the monkeys with MET. Surprisingly, DC-SIGN+ cells were found in the endometrium in most (but not all) animals with MET, although in others groups these cells were absent. We conclude that the rhesus monkey could be considered as a potential model for monitoring in vivo changes in endometrial receptivity and embryo invasion, which may lead to the identification of better specific markers for the window of implantation. PUBLICATIONS: None.