A PRIMATE IN VITRO IMPLANTATION MODEL

$30,981P51FY2010RRNIH

University Of Wisconsin-Madison, Madison WI

Investigators

Linked publications & trials

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To define the interactions between preimplantation embryos and maternal endometrial immune cells. One of the greatest gaps in our knowledge of human development is at the time of embryo implantation at the initiation of pregnancy, due to limitations on the experimental use of human embryos. In the parent grant, we proposed to adapt this paradigm and expand it to an in vitro implantation model with IVF-produced rhesus monkey embryos with 2 specific aims: to define trophoblast differentiation with rhesus monkey embryos in 3-dimensional extracellular matrix environments, and to determine the effects of 3-dimensional effector cells and selected growth factors on trophoblast differentiation. We have made substantial progress and have demonstrated that there is a significant impact of maternal monocytes, macrophages and NK cells on embryo development. In this administrative supplement, we will conduct three additional experiments. Experiment 1. To extend the study of maternal immune cell effects on embryo development to monocyte, macrophage and dendritic cell interactions with NK cells in regulation of cytokine secretion. Experiment 2. To define the effects of pregnancy hormones on leukocyte cytokine secretion. Experiment 3. To determine the effects of conditioned medium from monocytes, macrophages, dendritic cells and NK cells on cytokine secretion by cultured blastocysts. We will thus extend the significance of the parent grant and accelerate the development of new paradigms for studying primate-specific cellular and molecular events at embryo implantation. This research used WNPRC Animal, Research, Assay, and Immunology &Virology Services.

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