Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
J Steroid Biochem Mol Biol. 2023 Jun;230:106278. doi: 10.1016/j.jsbmb.2023.106278. Epub 2023 Mar 3.
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.
多囊卵巢综合征（PCOS）是一种影响女性生殖健康的系统性内分泌疾病。PCOS 患者的卵巢血管生成异常，表现为卵巢基质血管化增加和上调的促血管生成因子，如血管内皮生长因子（VEGF）。然而，PCOS 中这些变化的具体机制尚不清楚。在本研究中，我们诱导前脂肪细胞 3T3-L1 细胞的脂肪生成分化，发现脂肪细胞来源的外泌体通过递送 miR-30c-5p 促进人卵巢微血管内皮细胞（HOMEC）的增殖、迁移、管形成和 VEGFA 表达。机制上，双荧光素酶报告基因检测表明，miR-30c-5p 直接靶向细胞因子信号转导抑制因子 3（SOCS3）mRNA 的 3'-非翻译区（UTR）。此外，脂肪细胞来源的外泌体 miR-30c-5p 通过靶向 SOCS3 激活 HOMECs 中的信号转导子和转录激活子 3（STAT3）/VEGFA 通路。体内实验表明，通过 miR-30c-5p，尾静脉注射脂肪细胞来源的外泌体可加剧 PCOS 小鼠的内分泌和代谢紊乱以及卵巢血管生成。总之，该研究揭示了脂肪细胞来源的外泌体 miR-30c-5p 通过 SOCS3/STAT3/VEGFA 通路促进卵巢血管生成，从而参与 PCOS 的发生发展。
