Acupuncture alleviates premature ovarian insufficiency via Rictor/mTOR pathway in mice by stimulating the Guanyuan acupoint.

Abstract

Acupuncture is a popular therapeutic therapy for premature ovarian insufficiency (POI). The specific effect and the underlying mechanism of Guanyuan acupoint on the ovarian function of POI model mice remain unclear. The female C57BL6 mice were injected peritoneally with 12 mg/kg busulfan and 120 mg/kg cyclophosphamide to induce POI. The acupuncture intervention at Guanyuan acupoint was performed on the second day after the modeling. Vaginal smears were used to monitor the estrous cycle. The hematoxylin and eosin (H&E) staining was used to observe the morphological changes of ovarian tissue, and the TUNEL fluorescence staining assay was carried out to detect the apoptotic level of granulosa cells. The sex hormone levels were monitored as well. RNA sequencing was performed to select candidate gene which was regulated by acupuncture. Finally, the upstream lactating modification mechanism of Rictor was further investigated. The results showed that acupuncture at Guanyuan acupoint increased the number of vaginal exfoliated cells and inhibited the apoptosis of granulosa cell in POI model mice. Sex hormone levels indicated a marked decrease in AMH and Ein POI group, with a concurrent significant rise in FSH levels. Furthermore, the Rictor/mTOR pathway was inactivated in POI model group, while was prominently activated by acupuncture at Guanyuan acupoint. Acupuncture intervened H3K18la to increase Rictor promoter activity in POI. In conclusion, acupuncture at Guanyuan acupoint increased body and ovarian weight, improved ovarian tissue morphology and structure, improved follicle development, and regulated ovarian function in POI model mice. This might be related to the activation of the Rictor/mTOR pathway.