Acupuncture regulates the apoptosis of ovarian granulosa cells in polycystic ovarian syndrome-related abnormal follicular development through LncMEG3-mediated inhibition of miR-21-3p.
Acupuncture regulates the apoptosis of ovarian granulosa cells in polycystic ovarian syndrome-related abnormal follicular development through LncMEG3-mediated inhibition of miR-21-3p.
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DOI：
10.1186/s40659-023-00441-6
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发表时间：
2023-06-12
影响因子：
6.7
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中科院分区：
文献类型：
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多囊卵巢综合征（PCOS）的主要特征是卵泡发育异常和排卵功能障碍，这是由卵巢颗粒细胞过度凋亡引起的。针灸已被证明可以改善多囊卵巢综合征患者的卵泡发育异常，但其机制尚不清楚。本研究假设针刺对PCOS患者卵泡发育异常的作用机制是通过lnncmeg3介导的miR-21-3p调控抑制颗粒细胞凋亡。采用皮下注射脱氢表雄酮（DHEA）建立pcos样大鼠模型。针刺大鼠15 d （CV-4、RN-3、CV-6、SP-6、ex - ca1）。HE染色观察卵巢形态，ELISA法检测性激素和AMH水平。从各组大鼠中分离原代颗粒细胞，以评估针刺治疗、lnccmeg3、miR-21-3p与PCOS大鼠颗粒细胞凋亡的关系。lnccmeg3和miR-21-3p在PCOS大鼠卵巢颗粒细胞中高表达，lnccmeg3介导的miR-21-3p调控参与了PCOS大鼠的发生。MEG3沉默可减轻PCOS大鼠性激素失调和卵巢组织病理改变，促进卵泡细胞发育成熟。此外，沉默MEG3可提高颗粒细胞的活力和数量。此外，沉默MEG3可进一步抑制PCOS大鼠卵巢颗粒细胞的早期和晚期凋亡。针刺改善多囊卵巢大鼠多囊卵巢形态及性激素水平。针刺干预可提高颗粒细胞的活力和数量。针刺干预通过lnccmeg3靶向miR-21-3p抑制PCOS大鼠卵巢颗粒细胞的早期和晚期凋亡。上述结果提示针刺可下调lnncmeg3，从而靶向调控miR-21-3p，抑制颗粒细胞早、晚期凋亡，使其增殖正常化。这些因素最终补偿了卵泡发育异常。这些发现揭示了针灸作为一种安全治疗多囊卵巢综合征卵泡发育异常的临床潜力。lnccmeg3介导的miR-21-3p抑制调控卵巢颗粒细胞凋亡。lnccmeg3和miR-21-3p参与了pcos相关卵泡发育异常的发生发展。CuONPs诱导自噬激活和自噬通量阻断共存。针刺可改善多囊卵巢综合征患者的性激素水平和卵泡发育。揭示针刺治疗多囊卵巢综合征（PCOS）卵泡发育异常的潜在机制。
The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p. A PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS. LncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3. These results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS. LncMEG3-mediated inhibition of miR-21-3p regulates ovarian granulosa cell apoptosis. LncMEG3 and miR-21-3p are involved in the occurrence and development of PCOS-related abnormal follicular development. CuONPs induce co-occurrence of autophagy activation and autophagic flux blockade. Acupuncture can improve the sex hormone levels and follicular development in the context of PCOS. The underlying mechanism of acupuncture in the treatment of PCOS abnormal follicular development was revealed.