Melatonin inhibits endometriosis development by disrupting mitochondrial function and regulating tiRNAs

Sunwoo Park, Jiyeon Ham, Changwon Yang, Wonhyoung Park, Hahyun Park, Garam An, Jisoo Song, Taeyeon Hong, Soo Jin Park, Hee Seung Kim, Gwonhwa Song, Whasun Lim

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14 Scopus citations


Endometriosis is a benign gynecological disease characterized by abnormal growth of endometrial-like cells outside the uterus. Melatonin, a hormone secreted by the pineal gland, has been shown to have therapeutic effects in various diseases, including endometriosis. However, the underlying molecular mechanisms are yet to be elucidated. The results of this study demonstrated that melatonin and dienogest administration effectively reduced surgically induced endometriotic lesions in a mouse model. Melatonin suppressed proliferation, induced apoptosis, and dysregulated calcium homeostasis in endometriotic cells and primary endometriotic stromal cells. Melatonin also caused mitochondrial dysfunction by permeating through the mitochondrial membrane to disrupt redox homeostasis in the endometriotic epithelial and stromal cells. Furthermore, melatonin affected oxidative phosphorylation systems to decrease ATP production in End1/E6E7 and VK2/E6E7 cells. This was achieved through messenger RNA-mediated downregulation of respiratory complex subunits. Melatonin inhibited the PI3K/AKT and ERK1/2 pathways and the mitochondria-associated membrane axis and further suppressed the migration of endometriotic epithelial and stromal cells. Furthermore, we demonstrated that tiRNAGluCTC and tiRNAAspGTC were associated with the proliferation of endometriosis and that melatonin suppressed the expression of these tiRNAs in primary endometriotic stromal cells and lesions in a mouse model. Thus, melatonin can be used as a novel therapeutic agent to manage endometriosis.

Original languageEnglish
Article numbere12842
JournalJournal of Pineal Research
Issue number1
StatePublished - Jan 2023

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© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • antiproliferation
  • endometriosis
  • melatonin
  • mitochondria
  • tiRNA


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