title: Use of the progesterone receptor antagonist RU 486 to identify novel progesterone receptor-regulated pathways in implantation.
abstract: The steroid hormone progesterone (P) is a critical regulator of embryo implantation and maintenance of pregnancy. P acting through the nuclear progesterone receptors (PRs) regulates the expression of specific gene networks that in turn control the extensive cell proliferation, differentiation, and remodeling that occur in various uterine cell types during the progressive phases of implantation. To identify the P-regulated pathways that underlie the implantation process in the mouse, we employed RU 486, a well-characterized PR antagonist that binds to the receptor and blocks its gene regulatory function. We performed messenger RNA (mRNA) profiling in the peri-implantation uterus using oligonucleotide microarrays to analyze changes in mRNA levels in response to RU 486. This analysis provided, for the first time, a comprehensive profile of PR-regulated gene networks with potential roles during implantation. Our study identified a variety of novel PR-regulated molecules, such as growth factors, protease inhibitors, metabolic enzymes, peptide hormones, transcription factors, immune response molecules, cytoskeletal proteins, and cell adhesion molecules, that are potential mediators of P action in the peri-implantation mouse uterus. This article provides a brief description of the expression and function of these newly identified molecular pathways.
authors.affiliation: Department of Veterinary Biosciences and Molecular & Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA. ibagchi@uiuc.edu
authors.forename: Indrani C
authors.initials: IC
authors.lastname: Bagchi
authors.forename: Quanxi
authors.initials: Q
authors.lastname: Li
authors.forename: Yong-Pil
authors.initials: YP
authors.lastname: Cheon
authors.forename: Srinivasa Raju
authors.initials: SR
authors.lastname: Mantena
authors.forename: Athilakshmi
authors.initials: A
authors.lastname: Kannan
authors.forename: Milan K
authors.initials: MK
authors.lastname: Bagchi
mesh_terms: D000818:Animals; D003656:Decidua / Q000502:physiology; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011374:Progesterone / Q000502:physiology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015854:Up-Regulation; D014599:Uterus / Q000502:physiology
chemical_list: D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone