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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 1: 13 - 21

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.01.002

Electroacupuncture enhances the mitophagy of granulosa cells in premature ovarian insufficiency model mice by inactivating the hippo-yes-associated protein/transcriptional co-activator with postsynaptic density protein, drosophila disc large tumor suppressor, and zonula occludens-1 protein binding motif pathway

  • Jiaman WU ,
  • Meng TANG ,
  • Yu LUO ,
  • Haimin ZHU ,
  • Tianqi ZHAO ,
  • Fei MA ,
  • Yan NING
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  • 1 Department of Chinese Medicine, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen 518028, China
    2 Guangzhou University of Chinese Medicine, Guangzhou 510405, China
    3 Southern Medical University, Guangzhou 510515, China

Received date: 2023-11-22

  Accepted date: 2024-04-25

  Online published: 2025-01-10

Supported by

Shenzhen Science and Innovation Commission: Investigating the Mechanism of Action of Acupuncture in Regulating the Gut Microbiome to Inhibit Apoptosis of Ovarian Granulosa Cells in Premature Ovarian Insufficiency Mice based on the Rictor/Torepamycin Target Protein c2 Pathway(JCYJ20210324130001004);Sanming Project of Medicine in Shenzhen: the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Luo Songping National Famous Chinese Medicine Practitioner Female Reproductive Disorders Prevention and Treatment Team(SZZYSM202311010)

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Abstract

OBJECTIVE: To investigate the potential mechanism of electroacupuncture (EA) in alleviating premature ovarian insufficiency (POI) and to provide a theoretical basis for EA treatment of POI.

METHODS: For this purpose, a POI mice model was developed by injecting 12 mg/kg busulfan and 120 mg/kg cyclophosphamide intraperitoneally to induce POI. It was then proceeded by EA intervention at Guanyuan (CV4) acupoint on the second day following modeling. Similarly, apoptosis in ovarian granulosa cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, while enzyme-linked immunosorbent assay was employed for measuring serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and anti-müllerian hormone (AMH) levels. Moreover, transmission electron microscopy (TEM) was employed for examining mitochondrial morphology, while autophagy and hippo-yes-associated protein/transcriptional co-activator with postsynaptic density protein, drosophila disc large tumor suppressor, and zonula occludens-1 protein binding motif (YAP/TAZ) pathway related protein levels in ovarian tissue were detected via Western blotting.

RESULTS: Analysis of serum levels of various hormones indicated that serum FSH and LH were reduced in EA compared to the POI group, while E2 and AMH levels were found to be elevated in EA compared to the POI group. The EA was found to inhibit apoptosis in granulosa cells in POI model mice, in addition to improved mito-chondrial damage and significantly improved mitophagy. Pathway analysis revealed that EA was involved in activating the hippo-YAP/TAZ pathway, followed by reversing EA effects on granulosa cell apoptosis and mitophagy with the use of verteporfin, an autophagy and YAP-T-cell factor/enhancer of split and activator of transcription domain family member interaction inhibitor.

CONCLUSIONS: EA at the Guanyuan (CV4) acupoint protected the granulosa cell by inhibiting cell apoptosis and promoting mitophagy, which was mediated by the Hippo-YAP/TAZ pathway.

Key words： primary ovarian insufficiency; acupuncture; point CV4 (Guanyuan); mitophagy; hippo signaling pathway

Cite this article

Jiaman WU , Meng TANG , Yu LUO , Haimin ZHU , Tianqi ZHAO , Fei MA , Yan NING . Electroacupuncture enhances the mitophagy of granulosa cells in premature ovarian insufficiency model mice by inactivating the hippo-yes-associated protein/transcriptional co-activator with postsynaptic density protein, drosophila disc large tumor suppressor, and zonula occludens-1 protein binding motif pathway[J]. Journal of Traditional Chinese Medicine, 2025 , 45(1) : 13 -21 . DOI: 10.19852/j.cnki.jtcm.2025.01.002

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