title: Elevated peritoneal fluid TNF-α incites ovarian early growth response factor 1 expression and downstream protease mediators: a correlation with ovulatory dysfunction in endometriosis.
abstract: Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis.
authors: Department of Obstetrics and Gynecology and Women's Health, The University of Missouri, Columbia, MO 65212, USA.
authors: Julie A
authors: JA
authors: Birt
authors: Henda
authors: H
authors: Nabli
authors: Julie A
authors: JA
authors: Stilley
authors: Emma A
authors: EA
authors: Windham
authors: Shellaine R
authors: SR
authors: Frazier
authors: Kathy L
authors: KL
authors: Sharpe-Timms
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D016022:Case-Control Studies; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D010060:Ovulation; D010447:Peptide Hydrolases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010447:Peptide Hydrolases