Effect of Electro-Acupuncture on Gut Microbiome in Cisplatin-Induced Premature Ovarian Failure Mice

Abstract Background Growing evidences showed that gut microbiota is associated with premature ovarian failure (POF). Many case reports had shown that electro-acupuncture was effective in the treatment of POF. However, there was little research on regulating gut microbiome of POF mice by electro-acupuncture. Therefore, this study aimed to verify whether electro-acupuncture could improve ovarian function and regulate gut microbiome in mice with POF. In addition, the therapeutic effects of electro-acupuncture at acupoints and non-acupoints were compared. Methods POF mice were established by injected intraperitoneally with cisplatin (2mg/kg) for 2 weeks. Guanyuan (CV4) and Sanyinjiao (SP6) were selected in the electro-acupuncture at acupoints group (EA group). Non-acupoints which around CV4 and SP6 were selected in the electro-acupuncture at non-acupoints group (EN group). EA group and EN group were treated for 3 weeks. The ovarian function was evaluated by assays of histopathological and molecular. Meanwhile, the gut microbiome of POF mice was detected by 16S rDNA sequencing. Results The results showed that EA could restore the estrous cycle and reduce the number of atresia follicles in POF mice. The levels of serum follicle stimulating hormone and luteinizing hormone were decreased by EA. As well as, the levels of serum estradiol, anti mullerian hormone and β-glucuronidase were increased by EA. The relative expressions of PI3K, AKT and mTOR were increased to promote the proliferation of ovarian cells in EA group. According to the results of 16S rDNA sequencing, we found that the diversity of gut microbiome in mice with POF was changed. However, the abundance and diversity of gut microbiome could be regulated by EA in POF mice. The relative abundance of beneficial bacteria was increased by EA. The KEGG pathway analysis showed that the gut microbiome which associated with estrogen signaling pathway, oocyte maturation and PI3K-AKT signaling pathway were regulated by EA. Conclusions EA could provide protection against cisplatin-induced ovarian damage. The abundance and diversity of probiotics could be increased by EA. Moreover, EA might treat POF via regulating the gut microbiome.