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Basal and Steroid Hormone-Regulated Expression of CXCR4 in Human Endometrium and Endometriosis

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Abstract

Endometriosis is associated with activation of local and systemic inflammatory mechanisms, including increased levels of chemokines and other proinflammatory cytokines. We have previously reported increased gene expression of chemokine receptor 4 (CXCR4), the receptor for CXCL12, in lesions of the rat model of endometriosis. The CXCR4-CXCL12 axis has been shown to have both immune (HIV infection, lymphocyte chemotaxis) and nonimmune functions, including roles in tissue repair, angiogenesis, invasion, and migration. There is evidence indicating that these mechanisms are also at play in endometriosis; therefore, we hypothesized that activation of the CXCR4-CXCL12 axis could be responsible, at least in part, for the survival and establishment of endometrial cells ectopically. Immunohistochemistry (IHC) showed that CXCR4 protein levels were significantly higher in endometriotic lesions compared to the endometrium of controls. Next, we determined basal gene and protein expression of CXCR4 and CXCL12 and regulation by estradiol (E2) and/or progesterone (P4) in endometrial cell lines using quantitative polymerase chain reaction (qPCR), and Western blots. Basal CXCR4 gene expression levels were higher in epithelial versus stromal cells; conversely, CXCL12 was expressed at higher levels in stromal vs epithelial cells. CXCR4 gene expression was significantly downregulated by ovarian steroid hormones in endometrial epithelial. These data suggest that steroid modulation of CXCR4 is defective in endometriosis, although the specific mechanism involved remains to be elucidated. These findings have implications for future therapeutic strategies specifically targeting the inflammatory component in endometriosis.

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Authors and Affiliations

  1. Department of Microbiology, Ponce School of Medicine, BOX 7004, Ponce, PR, 00731, USA

    Abigail Ruiz BS, Lynnette A. Ruiz BS, Perla Báez MT & Idhaliz Flores PhD

  2. Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, PR, USA

    Virgilio A. Salvo MD

  3. Department of Pathology, Ponce School of Medicine, Ponce, PR, USA

    Miosotis García MD

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  1. Abigail Ruiz BS
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  2. Virgilio A. Salvo MD
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  3. Lynnette A. Ruiz BS
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Correspondence to Idhaliz Flores PhD.

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Ruiz, A., Salvo, V.A., Ruiz, L.A. et al. Basal and Steroid Hormone-Regulated Expression of CXCR4 in Human Endometrium and Endometriosis. Reprod. Sci. 17, 894–903 (2010). https://doi.org/10.1177/1933719110379920

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