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Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility
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Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility

Published on: April 5, 2024

Possible pathophysiological roles of mitogen-activated protein kinases (MAPKs) in endometriosis

Osamu Yoshino1, Yutaka Osuga, Yasushi Hirota

  • 1Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo.

American Journal of Reproductive Immunology (New York, N.Y. : 1989)
|November 20, 2004
PubMed
Abstract

Insights

Mitogen-activated protein kinases (MAPKs) are involved in endometriosis progression. Inhibiting p38 and JNK reduced inflammatory cytokine secretion, while p38 showed higher activity in endometriotic tissues, suggesting a key role in the disease.

Area of Science:

  • Cellular and Molecular Biology
  • Reproductive Medicine
  • Inflammation Research

Background:

  • Endometriosis is characterized by local peritoneal inflammation.
  • Mitogen-activated protein kinases (MAPKs) are crucial in cellular signaling pathways.
  • Understanding MAPK involvement in endometriosis may reveal new therapeutic targets.

Purpose of the Study:

  • To investigate the phosphorylation of extracellular signal-regulated kinase (ERK), p38 MAPK (p38), and c-Jun N-terminal kinase (JNK) in endometriotic stromal cells.
  • To determine the pathophysiological roles of these MAPKs in endometriosis concerning proinflammatory substances.
  • To compare p38 phosphorylation levels in endometriotic and eutopic endometrial tissues.

Main Methods:

  • Endometriotic stromal cells were isolated and treated with interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha), and hydrogen peroxide (H2O2).
  • MAPK phosphorylation was assessed using Western blot analysis.
  • The effects of specific MAPK inhibitors (PD98059, SB202190, SP600125) on cytokine secretion (IL-6, IL-8) and cyclo-oxygenase-2 (COX-2) expression were evaluated.

Main Results:

  • IL-1beta, TNFalpha, and H2O2 significantly increased the phosphorylation of ERK, p38, and JNK in endometriotic cells.
  • Inhibitors of p38 (SB202190) and JNK (SP600125) reduced IL-1beta-induced IL-6 and IL-8 secretion.
  • Inhibitors of p38 (SB202190) and ERK (PD98059) decreased IL-1beta-induced COX-2 expression.
  • Significantly higher p38 phosphorylation rates were observed in endometriotic tissues compared to eutopic endometrial tissues.

Conclusions:

  • MAPKs, particularly p38, are activated in endometriotic cells and tissues.
  • These signaling pathways play a significant role in the inflammatory processes associated with endometriosis.
  • MAPKs may serve as critical intracellular signal transducers contributing to the pathophysiology of endometriosis.

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