Quercetin Inhibits Ectopic Lesion Formation in Mice by Modulating the MAT2A/PRMT5 Pathway through PPARγ Activation.

Objective: This study aimed to examine the impact of quercetin on a mouse model of endometriosis and elucidate its underlying mechanisms.

Methods: An endometriosis model was established using C57BL/6 mice, which were divided into three groups: 1) sham group, 2) model group, and 3) model group treated with daily gavage administration of 100 mg/kg/d quercetin. After three weeks, mice were euthanized, and histopathological examination was performed using hematoxylin and eosin (HE) staining. The microstructure of the lesions was examined using electron microscopy, and the expression level of Sadenosylmethionine (SAM) was measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the expressions of related proteins, such as the peroxisome proliferator-activated receptor-γ (PPARγ) and methionine adenosyl-transferase 2A (MAT2A), were analyzed via Western blotting. Immunohistochemistry was employed to evaluate the expressions of Ki67, vimentin, vascular endothelial growth factor (VEGF), and Caspase-1.

Results: The endometriosis mice model was successfully established and characterized by ectopic lesions displaying transparent or red vesicular or nodular features with a visible vascular network on the surface. In the model group, endometrial epithelial hyperplasia exhibited columnar morphology, increased mesenchymal cell numbers, and regular cell morphology. Conversely, in the medication group, endometrial stromal cell numbers were sparse, cell morphology was irregular, and numerous vacuoles were observed in the endometrial tissue, indicative of apoptotic cell morphology changes. In comparison to the sham group, no statistically significant alterations were observed in the expression levels of SAM (P > 0.05). Conversely, the expression of PPARγ exhibited a notable decline. MAT2A, PRMT5, cyclin D1, and C-MYC expressions were increased, and vimentin, Ki67, VEGF, and caspase-1 expressions were strongly positive, with statistically significant differences (P < 0.05). In contrast, compared to the model group, the quercetin intervention group exhibited significantly reduced ectopic lesion weights, increased PPARγ expression, and significantly reduced protein expression levels of MAT2A, PRMT5, SAM, cyclin D1, and C-MYC. Furthermore, expressions of vimentin, Ki67, VEGF, and caspase-1 were weakly positive, with statistically significant differences (P < 0.05).

Conclusion: Quercetin modulated the transcription of the MAT2A/PRMT5 gene by activating PPARγ activity, thereby influencing the ectopic implantation and growth of endometrial cells.