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Analysis of the role of the transcription factor C/EBPβ in controlling uterine functions during early pregnancy

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Title: Analysis of the role of the transcription factor C/EBPβ in controlling uterine functions during early pregnancy
Author(s): Ramathal, Cyril Y.
Director of Research: Bagchi, Milan K.
Doctoral Committee Chair(s): Katzenellenbogen, Benita S.
Doctoral Committee Member(s): Bagchi, Milan K.; Kemper, Byron W.; Freeman, Brian C.; Raetzman, Lori T.
Department / Program: Cell & Developmental Biology
Discipline: Cell and Developmental Biology
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Implantation infertility decidualization embryo uterus endometrium estrogen progesterone Extracellular matrix (ECM)
Abstract: Embryo implantation into the endometrium is a complex biological process involving the integration of steroid hormone signaling, endometrial tissue remodeling and maternal- fetal communications. A successful pregnancy is the outcome of the timely integration of these events during the early stages of implantation. The involvement of ovarian steroid hormones, estrogen (E) and progesterone (P), acting through their cognate receptors, is essential for uterine functions during pregnancy. The molecular mechanisms that control the process of implantation are undergoing active exploration. Through our recent efforts, we identified the transcription factor, CCAAT Enhancer Binding Protein Beta (C/EBPb) as a prominent target of estrogen and progesterone signaling in the uterus. The development of a C/EBPb-null mouse model, which is infertile, presented us with an opportunity to analyze the role of this molecule in uterine function. We discovered that C/EBPb functions in two distinct manners: (i) by acting as a mediator of E-induced proliferation of the uterine epithelium and (ii) by controlling uterine stromal cell differentiation, a process known as decidualization, during pregnancy. My studies have delineated important mechanisms by which E regulates C/EBPb expression to induce DNA replication and prevent apoptosis of uterine epithelial cells during E-induced epithelial growth. In subsequent studies, I analyzed the role of C/EBPb in decidualization and uncovered a unique mechanism by which C/EBPb regulates the synthesis of a unique laminin-containing extracellular matrix (ECM) that supports stromal cell differentiation and embryo invasion. In order to better define the role of laminin in implantation, we developed a laminin gamma 1-conditional knockout mouse model. This is currently an area of ongoing investigation. The information gained from our analysis of C/EBPb function in the uterus provides new insights into the mechanisms of steroid hormone action during early pregnancy. Ultimately, our findings may aid in the understanding of dysregulation of hormone-controlled pathways that underlie early pregnancy loss and infertility in women.
Issue Date: 2010-05-14
URI: http://hdl.handle.net/2142/15569
Rights Information: Chapter 1, copyrighted by Thieme Medical Publishers Chapter 2, copyrighted by American Society of Microbiology.
Date Available in IDEALS: 2010-05-14
2012-06-08
Date Deposited: May 2010
 

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