Effects of Exosomes Derived From Eutopic Endometrial Cells in Endometriosis and the Discovery of Related Serum miRNA Biomarkers for Endometriosis

Abstract

Objective: Exosomes are secreted by most cell types and reflect the internal state of their cells of origin, playing crucial roles in the progression of various pathological conditions. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue outside the uterus, including in the ovaries, fallopian tubes, and peritoneal cavity. It primarily affects women of reproductive age and is often associated with infertility. Despite its high prevalence, the underlying pathogenesis remains poorly understood, and the high recurrence rate highlights the urgent need for reliable, non-invasive biomarkers for early diagnosis. Although exosomes have been implicated in the pathophysiology of endometriosis-particularly in processes such as angiogenesis and immune modulation-their role in regulating cell proliferation and apoptosis remains poorly understood.

Method of study: We collected eutopic endometrial tissues from patients with endometriosis (EMS-EM) and without endometriosis (CTL-EM) and cultured to primary cells. Exosomes were extracted from EMS-EM and CTL-EM, respectively, and then treated the EMS-EM cells for 24 h.

Results: CCK-8 and FACS assays showed that exosomes extracted from EMS-EM (EMS-Exo) treatment induced cell proliferation and reduced apoptosis. In particular, JC-1 red/green dye was significantly increased, and the mitochondrial apoptosis signal pathway was regulated by EMS-Exo treatment. The examination of protein expression identified that proliferation was induced through ERK and AKT signaling, and the mitochondrial apoptosis signaling pathway was regulated through the PI3K/AKT mechanism. miRNA array analysis showed differences in 16 miRNAs, with miR-200a-3p upregulated and 29a-3p downregulated. qRT-PCR was performed on serum exosomes for in vivo diagnosis, and significant differences were observed in five miRNAs. Through ROC curve analysis, the combination of three miRNAs was derived to show the highest diagnostic performance.

Conclusions: These findings suggest that the exosome-related mechanism influences the development of endometriosis and highlights the potential of exosomes as novel diagnostic biomarkers for endometriosis.