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Abstract
Grant Number: 5U01HD042311-04 Project Title: Molecular Analysis of Uterine Receptivity
PI Information: Name Title DEMAYO, FRANCESCO fdemayo@bcm.tmc.edu PROFESSOR Abstract: The overall objective of this proposal is to define the essential molecular mechanisms that underlie uterine receptivity. Ovarian-derived progesterone is known to be an indispensable signaling molecule in the preparation of the uterus for embryo attachment and subsequent invasion Using the progesterone receptor knockout mouse in combination with DNA microarray technology, we recently demonstrated that the morphogen, Indian hedgehog, Ihh, is expressed in the murine uterus and, importantly, regulated by progesterone via its nuclear receptor. This important observation forms the basis of the following hypothesis: The Indian hedgehog signaling pathway is an integral regulatory axis for the preparation of the uterus for embryonic implantation. This proposal will establish a novel mouse model for the reproductive tissue specific ablation of Ihh and then evaluate the impact of Ihh ablation on uterine function. Then, this proposal will investigate the expression of members of the Ihh signaling cascade in human endometrial tissue. Then, this proposal will investigate the expression of members of the Ihh signaling cascade in human endometrial tissue. The goals of this proposal will be achieved by using Homologous recombination in ES cells to insert Cre recombinase into the progesterone receptor locus. This mouse will be used to ablate Ihh specifically in the uterus and mouse reproductive tissues. The physiologic and molecular impact of Ihh ablation in the uterus will then be investigated. Finally the expression of Ihh in the receptive and non-receptive human endometrium will be investigated. The contribution of this proposal to the U01 consortium will be the establishment of a novel animal model that will facilitate the investigation of the role of regulatory molecule sin uterine receptivity, as well as, the investigation of the role and expression of members of the Ihh signaling cascade in mouse and human receptivity.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
embryo implantation, gene targeting, genetic model, genetic regulation, genetically modified animal, model design /development, uterus
biological signal transduction, cooperative study, gene expression, hormone regulation /control mechanism, progesterone receptor, women's health
RNase protection assay, bioengineering /biomedical engineering, biopsy, biotechnology, embryonic stem cell, female, human subject, immunocytochemistry, in situ hybridization, laboratory mouse, microarray technology, young adult human (21-34)
Institution: BAYLOR COLLEGE OF MEDICINE 1 BAYLOR PLAZA HOUSTON, TX 770303498 Fiscal Year: 2005 Department: MOLECULAR AND CELLULAR BIOLOGY Project Start: 01-APR-2002 Project End: 31-MAR-2007 ICD: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT IRG: ZHD1