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Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators: A Correlation With Ovulatory Dysfunction in Endometriosis

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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.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Women’s Health, Division of Reproductive and Perinatal Research, The University of Missouri, Columbia, 1 Hospital Drive, NW 507 SOM, DC051.00, 65212, Columbia, MO, USA

    Julie A. Birt MS, Henda Nabli MS, Julie A. Stilley PhD, Emma A. Windham & Kathy L. Sharpe-Timms PhD

  2. Division of Animal Sciences, College of Agriculture, Food and Natural Resources, The University of Missouri, Columbia, MO, USA

    Julie A. Birt MS, Julie A. Stilley PhD & Kathy L. Sharpe-Timms PhD

  3. Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, MO, USA

    Shellaine R. Frazier DO

Authors
  1. Julie A. Birt MS
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  2. Henda Nabli MS
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  3. Julie A. Stilley PhD
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  4. Emma A. Windham
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  5. Shellaine R. Frazier DO
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  6. Kathy L. Sharpe-Timms PhD
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Correspondence to Kathy L. Sharpe-Timms PhD.

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Birt, J.A., Nabli, H., Stilley, J.A. et al. Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators: A Correlation With Ovulatory Dysfunction in Endometriosis. Reprod. Sci. 20, 514–523 (2013). https://doi.org/10.1177/1933719113477479

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