Melatonin inhibits endometriosis development by disrupting mitochondrial function and regulating tiRNAs

Area of Science:

• Gynecology
• Molecular Biology
• Endocrinology

Background:

• Endometriosis is a common benign gynecological condition with abnormal endometrial-like tissue growth outside the uterus.
• Melatonin, a pineal gland hormone, exhibits therapeutic potential, but its mechanisms in endometriosis require elucidation.
• Current treatments for endometriosis have limitations, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the molecular mechanisms underlying melatonin's therapeutic effects on endometriosis.
• To evaluate the efficacy of melatonin in reducing endometriotic lesions and suppressing cell activity.
• To explore the role of specific tiRNAs in endometriosis proliferation and melatonin's impact on them.

Main Methods:

• Utilized a surgically induced mouse model of endometriosis.
• Administered melatonin and dienogest to assess lesion reduction.
• Analyzed endometriotic cell proliferation, apoptosis, calcium homeostasis, and mitochondrial function.
• Investigated melatonin's effects on oxidative phosphorylation, signaling pathways (PI3K/AKT, ERK1/2), and cell migration.
• Examined the expression of tiRNA^GluCTC and tiRNA^AspGTC in response to melatonin.

Main Results:

• Melatonin and dienogest significantly reduced endometriotic lesion size in the mouse model.
• Melatonin suppressed endometriotic cell proliferation, induced apoptosis, and dysregulated calcium homeostasis.
• Melatonin impaired mitochondrial function, disrupted redox homeostasis, and decreased ATP production.
• Melatonin inhibited PI3K/AKT and ERK1/2 pathways, suppressed cell migration, and affected mitochondria-associated membranes.
• Melatonin downregulated tiRNA^GluCTC and tiRNA^AspGTC expression, which are linked to endometriosis proliferation.

Conclusions:

• Melatonin demonstrates significant therapeutic potential for endometriosis by targeting multiple cellular processes.
• The mechanisms involve suppression of proliferation, induction of apoptosis, mitochondrial dysfunction, and inhibition of key signaling pathways.
• Melatonin's ability to modulate specific tiRNAs offers a novel therapeutic avenue for managing endometriosis.