Date of Award
Doctor of Philosophy (PhD)
Professor David A. Clark
There is a high rate of pregnancy failure in humans. The greatest loss occurs at the time of implantation or immediately after the embryo has implanted. Up to 50-60% of this loss can be attributed to embryonic chromosomal abnormalities. The absence or anomalous amounts of physiologic factors which are necessary for implantation and early embryonic development may be the cause of pregnancy failure. Since the embryo is foreign, it is specifically necessary to explore the role of rejection and failure of mechanisms that suppress rejection at implantation.
The murine system has been used to investigate the identity of immunosuppressive molecules produced during the process of preimplantation embryo development. Supernatants from mouse in vitro fertilized (IVF) embryo cultures can suppress in vitro lymphocyte proliferation stimulated by the mitogen concanavalin A. Medium conditioned by incubation with mouse epididymal spermatozoa alone were even more inhibitory to mitogen stimuhued lymphocyte proliferation. Thin layer chromatography detected the polyamines spermine in sperm, and spermidine as well as spermine in IVF embryo culture supernatants. Evidence was obtained that these were possibly the ill vitro molecules that were immunosuppressive and were likely produced by the embryo. The diamine putrescine was also detected but was not immunosuppressive.
The conclusion from the studies suggest that polyamines may have a role in vivo in suppressing uterine immune response thereby assisting the embryo in the process of implantation. Failure of embryos to produce sufficient amounts of polyamines perhaps due to chromosome abnormalities, may explain failure of embryo implantation. As well, the failure of IVF embryos to produce adequate quantities of polyamines which are known to be essential for cell proliferation, could lead to embryo division arrest. In this broad sense polyamines may be viewed as "growth factors" i.e. defined molecules essential for cell division.
Porat, Offie, "Putative Immunosuppressive Molecules Associated with In Vitro Fertilized Embryos may be Essential Growth Factors" (1990). Open Access Dissertations and Theses. Paper 2678.