Electroacupuncture alleviates polycystic ovary syndrome-like symptoms through improving insulin resistance, mitochondrial dysfunction, and endoplasmic reticulum stress via enhancing autophagy in rats

Abstract

Background: Electroacupuncture (EA), a treatment derived from traditional Chinese medicine, can effectively improve hyperandrogenism and insulin resistance in patients with polycystic ovary syndrome (PCOS), however, its underlying mechanisms remain obscure. This study aimed to investigate whether EA could mitigate PCOS-like symptoms in rats by regulating autophagy. Methods: A rat model of PCOS-like symptoms was established by subcutaneous injection with dehydroepiandrosterone (DHEA), and then EA treatment at acupoints (ST29 and SP6) was carried out for 5 weeks. To inhibit autophagy in rats, intraperitoneal injection with 0.5 mg/kg 3-MA (an autophagy inhibitor) was performed at 30 min before each EA treatment. Results: EA intervention alleviated PCOS-like symptoms in rats, which was partly counteracted by the combination with 3-MA. Moreover, DHEA-exposure-induced deficient autophagy in skeletal muscle was improved by EA treatment. EA-mediated improvements in insulin resistance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in PCOS-like rats were counteracted by 3-MA pretreatment. Mechanically, EA attenuated autophagy deficiency-mediated insulin resistance in PCOS-like rats via inactivating mTOR/4E-BP1 signaling pathway. Conclusions: Taken together, our findings indicate that EA treatment ameliorates insulin resistance, mitochondrial dysfunction, and ER stress through enhancing autophagy in a PCOS-like rat model. Our study provides novel insight into the mechanisms underlying the treatment of EA in PCOS, which offers more theoretic foundation for its clinical application.

miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome

“…PCOS, characterized by such inconvenient symptoms as irregular menstrual bleeding and infertility, has been regarded as a "nuisance disease'' devoid of effective therapeutic strategies (Conway et al, 2014;Peng et al, 2020). Inhibition of granulosa cell survival provides a novel insight into PCOS treatment (Zhong et al, 2018;Cox et al, 2020).…”

The Complementary and Alternative Medicine for Polycystic Ovary Syndrome: A Review of Clinical Application and Mechanism

“…Similarly, some studies have shown that EA can correct the imbalance of FSH and AMH in PCOS granulosa cells by inhibiting the excessive secretion of AMH, thus improving hyperandrogenemia and follicular development stagnation [ 22 ]. Peng et al concluded that EA can improve IR, mitochondrial dysfunction, and ER by enhancing autophagy in PCOS-like rats [ 23 ].…”

Effect of Acupuncture on Polycystic Ovary Syndrome in Animal Models: Study Protocol for a Systematic Review and Meta-Analysis

“…It is proved that acupuncture could play an important role in the regulation of hormone levels, ovulation induction, psychological regulation, and weight control [9,10]. Also, experiments on PCOS animal models showed that electrical acupuncture (EA) ameliorated insulin resistance and mitochondrial dysfunction by promoting autophagy [11]. EA regulates ovarian innervations to increase the numbers of preovulatory follicles in PCOS-like rats [12].…”