Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway

Li, Hongxiao; Shi, Lei; Liang, Shang-jie; Fang, Chen-Chen; Qian, Xu; Lu, Ge; Wang, Qian; Cheng, Jie; Shen, Jie; Shen, Mei-Hong

doi:10.1016/j.joim.2022.01.007

Cited by 13 publications

(13 citation statements)

References 39 publications

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“…In the present study, we established a DOR rat model via intragastric administration of TGs. Characterization of sex hormones in the serum, including estradiol (E2), follicle-stimulating hormone, and anti-Müllerian hormone (AMH), was confirmed in our previous studies ( Fang et al, 2019 ; Lu et al, 2021 ; Wang et al, 2021 ; Li et al, 2022 ). In addition, TG-induced DOR rats displayed disordered estrous cycles; decreased primordial follicles, primary follicles, and secondary follicles; increased atretic follicles; and differential expression of miRNAs when compared with normal rats.…”

Section: Discussionsupporting

confidence: 68%

“…The top 10 pathways regulated by DE miRNAs were the mTOR signaling pathway, MAPK signaling pathway, proteoglycans in cancer, pathways in cancer, human papillomavirus infection, Kaposi sarcoma-associated herpesvirus infection, sphingolipid signaling pathway, TNF signaling pathway, human immunodeficiency virus infection, and focal adhesion ( Figure 6C ). Our study demonstrated that restoring the PI3K/AKT signaling pathway could improve the ovarian reserve in DOR rats ( Li et al, 2022 ), and mTOR is a key downstream target of the PI3K/AKT pathway. Therefore, we further analyzed the mTOR signaling pathway to identify target genes.…”

Section: Resultsmentioning

confidence: 64%

“…The target genes for significant miRNAs in the ACU and DOR groups were predicted using TargetScan (Whitehead Institute for Biomedical Research, Cambridge, United States) ( Kim et al, 2021b ) and miRanda (Memorial Sloan-Kettering Cancer Center, New York, United States) ( Li et al, 2022 ). Target genes with context score percentiles ˂ 50 (by TargetScan) and maximum energy ˃ −10 (by miRanda) were cleaned up.…”

Section: Methodsmentioning

confidence: 99%

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Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Zhu

et al. 2022

Front. Genet.

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Acupuncture is widely used to improve ovarian function. Previously, we demonstrated that acupuncture can improve oxidative stress in rats with tripterygium glycoside tablet suspension (TG)-induced diminished ovarian reserve (DOR). Herein, we aimed to explore the antioxidation mechanism of acupuncture for ameliorating the ovarian reserve in DOR rats. We performed microRNA sequencing and bioinformatics analysis to screen differentially expressed miRNAs (DE miRNAs) in ovarian tissues. In total, 1,172 miRNAs were identified by miRNA sequencing, of which 28 DE miRNAs were detected (including 14 upregulated and 14 downregulated) in ovarian tissues from the acupuncture group when compared with the DOR model rats. Based on functional enrichment analysis, the target genes of DE miRNAs were significantly enriched in GO-biological process (BP) terms associated with biological processes, positive regulation of transcription by RNA polymerase II, signal transduction, regulation of transcription, DNA-templated processes, and oxidation–reduction processes. In the Kyoto Encyclopedia of Genes and Genomes analysis, the main pathways were the MAPK signaling pathway, hepatitis B, proteoglycans in cancer, human cytomegalovirus infection, and the Ras signaling pathway. Finally, reverse transcription-quantitative PCR results confirmed that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 were downregulated in the acupuncture group. The results revealed the impact of acupuncture on miRNA profiling of ovarian tissues from DOR rats, suggesting that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 might provide relevant cues to relieve DOR-mediated oxidative stress.

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Section: Discussionsupporting

confidence: 68%

Section: Resultsmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

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Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Zhu

et al. 2022

Front. Genet.

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“…Xiang et al [89] further found that EA improved oocyte quality and embryonic development potential by activating the IRS-1/ PI3K/GLUT4 signaling pathway. Li et al [90] verified this conclusion that moxibustion improved ovarian function and inhibited ovarian granulosa cell apoptosis by activating the PI3K/AKT signaling pathway. However, this conclusion has also had opposite results.…”

Section: Promotion Of Ovulationmentioning

confidence: 83%

The Application of Complementary and Alternative Medicine in Polycystic Ovary Syndrome Infertility

Shi

Wang

Zhu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Polycystic ovary syndrome (PCOS) is a lifelong reproductive endocrine disease, which is the most common cause of anovular infertility. Modern medicine mainly treats infertile patients with PCOS by improving living habits, ovulation induction therapy, and assisted reproductive technology (ART), but the effect is not satisfied. Complementary alternative medicine (CAM) has conspicuous advantages in the treatment of PCOS infertility due to its good clinical efficacy, wide mechanism of action, and no obvious adverse reactions, but its safety and effectiveness in the treatment of PCOS infertility have not been proved. Based on the existing clinical and experimental studies, this paper looks for the therapeutic effect and the mechanism behind it, and explores the safety and effectiveness of its treatment in PCOS infertility, in order to provide reference for future clinical treatment and experimental research.

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“…Similar to EA, moxibustion is another traditional Chinese medicine therapy that stimulates acupoints and meridians by applying heat from moxibustion fires, near-infrared stimulation, and special substances found in moxa smoke. Previous studies have demonstrated that moxibustion can enhance fertility in patients with diminished ovarian reserve function by acting on the reproductive system through various channels and targets [ 18 – 20 ]. However, it remains unclear whether moxibustion can improve the survival, migration, and therapeutic effects of MSCs.…”

Section: Introductionmentioning

confidence: 99%

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy

Lu,

Li,

Song

et al. 2024

Stem Cell Res Ther

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Background Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. Methods A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. Results A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. Conclusions Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients. Graphical abstract

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Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway

Cited by 13 publications

References 39 publications

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

The Application of Complementary and Alternative Medicine in Polycystic Ovary Syndrome Infertility

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy

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