Adipocyte-derived exosomal miR-30c-5p promotes ovarian angiogenesis in polycystic ovary syndrome via the SOCS3/STAT3/VEGFA pathway

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 230; p. 106278
• Main Authors: Hu, Jian, Lin, Fangyou, Yin, Yuchen, Shang, Yunjie, Xiao, Zhuoni, Xu, Wangming
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2023
• Subjects: Angiogenesis; Animals; Cell Proliferation - genetics; Endothelial Cells - metabolism; Exosomes; Female; Humans; Mice; MicroRNAs - genetics; MiR-30c-5p; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; SOCS3; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; STAT3/VEGFA pathway; Suppressor of Cytokine Signaling 3 Protein - genetics; Suppressor of Cytokine Signaling 3 Protein - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; DHEA; SFs; IHC; TRADD; HRP; Exosomes; ncRNAs; Angiogenesis; UTR; ECs; FBS; GCs; CCK-8; FSH; IF; PBS; Polycystic ovary syndrome; DAPI; PVDF; IL-6; HOMA-IR; SDS-PAGE; PCOS; AT; NTA; PFs; HUVECs; PCNA; miRNAs; STAT3/VEGFA pathway; ATCC; RIPA; DMEM; SD; SOCS3; FITC; T; EVs; MiR-30c-5p; VEGF; STAT3; CL; SNHG9; AFs; VEGFA; CFs; HOMECs; JAK; HE; TEM
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2023.106278

Polycystic ovary syndrome (PCOS) is a systemic endocrine disease affecting women's reproductive health. Ovarian angiogenesis in PCOS patients is abnormal, manifested by increased ovarian stromal vascularization and upregulated proangiogenic factors such as vascular endothelial growth factor (VEGF). However, the specific mechanisms underlying these changes in PCOS remain unknown. In this study, we induced the adipogenic differentiation in preadipocyte 3T3-L1 cells and found that adipocyte-derived exosomes promoted proliferation, migration, tube formation, and VEGFA expression in human ovarian microvascular endothelial cells (HOMECs) by delivering miR-30c-5p. Mechanistically, dual luciferase reporter assay demonstrated that miR-30c-5p directly targeted the 3'- untranslated region (UTR) of suppressor of cytokine signaling 3 (SOCS3) mRNA. In addition, adipocyte-derived exosomal miR-30c-5p activated signal transducer and activator of transcription 3 (STAT3)/VEGFA pathway in HOMECs via targeting SOCS3. In vivo experiments indicated that tail vein injection of adipocyte-derived exosomes exacerbated endocrine and metabolic disorders and ovarian angiogenesis in mice with PCOS via miR-30c-5p. Taken together, the study revealed that adipocyte-derived exosomal miR-30c-5p promotes ovarian angiogenesis via the SOCS3/STAT3/VEGFA pathway, thereby participating in the development of PCOS. •Adipocytes-derived exosomes participate in the development of PCOS.•miR-30c-5p activates the STAT3/VEGFA pathway by targeting SOCS3, thus promoting ovarian angiogenesis.•Intervention for exosomes is promising to develop new therapeutic strategies for PCOS.