description) The long-term goal of this project is to gain an understanding of the mechanism of platelet-activating factor's [1-O-alkyl-sn-acetyl-glycero-3-phosphocholine; PAF] action in the preimplantation embryo which facilitates implantation. PAF, a potent signaling phospholipid, has been implicated in a variety of reproductive processes. Embryo-derived PAF plays a crucial role in the establishment of pregnancy. However, the direct impact of PAF on preimplantation development is not known. The present proposal will attempt to address this issue with respect to the PAF-receptor mediated gene expression in CFW mouse embryos for the following reasons: First, 3H-PAF binds to CFW mouse embryos. In other sytems PAF through receptor interaction, induces phospholipase-C hydrolysis of phosphatidyl inositol 4,5-biphosphate to diacylglycerol and inositol 1,4,5-triphosphate, which results in calcium mobilization; and second, PAF exposure leads to increased blastocyst cell numbers suggesting that, analogous to observations in other cell systems, PAF can induce gene expression. The investigators hypothesize that embryo development involves the PAF stimulation of the embryonic receptor mediated inositol-triphosphate system and resultant gene expression thus affecting development. This highly reproducible murine-embryonic model presents the investigators with the opportunity to examine the extent by which PAF influences embryo development. There are three specific aims addressing these interests:
SPECIFIC AIM 1 is to determine the kinetics of [3H]PAF binding to CFW mouse preimplantation embryos.
SPECIFIC AIM 2 is to determine that CFW mouse preimplantation embryos express the PAF-receptor.
SPECIFIC AIM 3 is to determine that PAF increases intracellular calcium levels in CFW mouse embryos. This proposal is relevant to human reproduction since human embryos produce PAF and this embryo-derived PAF mediates the maternal recognition of pregnancy and PAF production by human embryos is related to their subsequent pregnancy potential.
| Logan, J E; Roudebush, W E (2000) Platelet-activating factor increases intracellular calcium levels in preimplantation stage embryos. Early Pregnancy 4:30-8 |
