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

Abstract

INTRODUCTION: 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. Histopathological examination was performed using hematoxylin and eosin (HE) staining. The microstructure of the lesions was examined using electron microscopy. The expressions levels of related proteins, such as the peroxisome proliferator- activated receptor-&#x3b3; (PPAR&#x3b3;), methionine adenosyl-transferase 2A (MAT2A), Ki67 and VEGF was measured using Western blotting or Immunohistochemistry. RESULTS: Compared to the model group, the medication group showed sparse endometrial stromal cells, irregular morphology, and numerous vacuoles, indicating apoptosis. Compared to the sham group, SAM expression was unchanged (P > 0.05), while PPAR&#x3b3; decreased. MAT2A, PRMT5, cyclin D1, and C-MYC increased, and vimentin, Ki67, VEGF, and caspase-1 were strongly positive (P < 0.05). Quercetin intervention reduced ectopic lesion weights, increased PPAR&#x3b3;, and decreased MAT2A, PRMT5, SAM, cyclin D1, and C-MYC. Vimentin, Ki67, VEGF, and caspase-1 were weakly positive (P < 0.05). DISCUSSION: These results indicate that quercetin effectively reduced endometriosis lesions by modulating key protein expressions and promoting apoptosis. CONCLUSION: Quercetin modulated the transcription of the MAT2A/PRMT5 gene by activating PPAR&#x3b3; activity, thereby influencing the ectopic implantation and growth of endometrial cells.