Authors

Eri Takai, M.D., Fuminori Taniguchi, M.D., Ph.D., Kazuomi Nakamura, M.Sc. Takashi Uegaki, M.D., Tomio Iwabe, M.D., Ph.D., Tasuku Harada, M.D., Ph.D.

Volume 100, Issue 4, Pages 1170-1178, October 2013

Abstract

Objective:

To evaluate the effects of parthenolide on human endometriotic cells and murine endometriotic lesions.

Design:

Experimental study.

Setting:

University hospital and laboratory of animal science.

Patient(s) and Animal(s):

Twenty women with ovarian endometrioma and 30 mice.

Intervention(s):

Ectopic endometrial tissue from the endometrioma was collected.

Main Outcome Measure(s):

Human endometriotic stromal cells (ESCs) were pretreated with parthenolide and exposed to tumor necrosis factor (TNF)-α. Interleukin 8 (IL-8) and COX-2 gene expressions were evaluated by real-time reverse transcription–polymerase chain reaction. Interleukin-8 protein, prostaglandin E2 (PGE2) level, and intranuclear p65 protein concentration were determined by ELISA. Cell proliferation was assessed by 5-bromo-2′-deoxyuridine–ELISA. Phosphorylation of signaling pathways in ESCs was evaluated by Western blotting. Gene expression and proliferative activity in murine endometriosis-like lesions were assessed by real-time reverse transcription–polymerase chain reaction and Ki67 staining, respectively.

Result(s):

With parthenolide pretreatment, TNF-α–induced IL-8 gene and protein expression in ESCs were diminished. Tumor necrosis factor α–induced COX-2 expression and PGE2 synthesis were also inhibited. Adding parthenolide repressed TNF-α–induced 5-bromo-2′-deoxyuridine incorporation and IκB phosphorylation in ESCs. As in vivo experiments, administering parthenolide reduced the number, surface area, and weight, the level of Vegf, Il-6, Mcp-1, and Lif gene expression, and the percentage of Ki67-positive cells in murine endometriosis-like lesions.

Conclusion(s):

Parthenolide repressed the development of endometriosis by suppressing the inflammatory peritoneal environment through the nuclear factor κB pathway.

Read the full text at: http://www.fertstert.org/article/S0015-0282(13)00728-0/fulltext