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LPAR2 and LPAR4 are the Main Receptors Responsible for LPA Actions in Ovarian Endometriotic Cysts

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Abstract

Endometriosis has been considered as an estrogen (E2)-dependent and progesterone (P4)-resistant disease. On the other hand, lysophosphatidic acid (LPA) has been suggested as a significant modulator of ovarian pathology, acting via both LPA levels and LPA receptor (LPAR) upregulation. Therefore, the objective of the present study was to evaluate LPA concentration as well as LPARs, autotaxin (ATX), and phospholipase A2 (PLA2) expression in ovarian endometriotic cysts and normal endometrium with correlation of the expression of E2 and P4 receptors in endometriotic cysts. The analyses were carried out using the tissues derived from 37 patients with ovarian endometriosis and 20 endometrial samples collected from women without endometriosis were used as a control. We found that ovarian endometriotic cysts are a site of LPA synthesis due to the presence of enzymes involved in LPA synthesis in the tissue. Additionally, when we compared endometriotic cysts versus normal endometrium, we were able to show overexpression of 3 from 6 examined LPARs and both enzymes responsible for LPA synthesis in endometriotic cysts. Finally, we found the correlations between LPARs, ATX, and PLA2 and the expression of E2 and P4 receptors in endometriotic cysts. Owing to the high LPAR2 and LPAR4 transcript and protein expression in endometriotic ovarian cysts and positive correlations of both these receptors with the PR-B and ERb, respectively, those receptors seem to be the most promising predictors of the endometriotic cysts as well as the main receptors responsible for LPA action in the ovarian endometriosis.

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Authors and Affiliations

  1. Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland

    Ilona Kowalczyk-Zieba PhD, Izabela Woclawek-Potocka DVM, PhD, DrSci, Dorota Boruszewska PhD, Katarzyna Grycmacher MSc, Emilia Sinderewicz MSc & Joanna Staszkiewicz MSc

  2. Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Warmia and Masuria, Olsztyn, Poland

    Tomasz Wasniewski MD

  3. Department of Reproduction and Gynecological Endocrinology, Faculty of Medicine, Medical University of Bialystok, Skłodowskiej-Curie 24a., 15-276, Białystok, Poland

    Slawomir Wolczynski

  4. Department of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Białystok, Poland

    Slawomir Wolczynski

Authors
  1. Ilona Kowalczyk-Zieba PhD
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  2. Izabela Woclawek-Potocka DVM, PhD, DrSci
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  3. Tomasz Wasniewski MD
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  4. Dorota Boruszewska PhD
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  5. Katarzyna Grycmacher MSc
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  6. Emilia Sinderewicz MSc
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  7. Joanna Staszkiewicz MSc
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  8. Slawomir Wolczynski
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Correspondence to Slawomir Wolczynski.

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Kowalczyk-Zieba, I., Woclawek-Potocka, I., Wasniewski, T. et al. LPAR2 and LPAR4 are the Main Receptors Responsible for LPA Actions in Ovarian Endometriotic Cysts. Reprod. Sci. 26, 139–150 (2019). https://doi.org/10.1177/1933719118766263

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  • DOI: https://doi.org/10.1177/1933719118766263

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