[Effect of acupuncture on the oxeiptosis Kelch-like ECH-associated protein 1/phosphoglycerate mutase 5/mitochondrial apoptosis-inducing factor 1 signaling pathway in rats with diminished ovarian reserve].

Objectives: To observe the effect of acupuncture on the oxeiptosis Kelch-like ECH-associated protein 1 (KEAP1)/phosphoglycerate mutase 5 (PGAM5)/mitochondrial apoptosis-inducing factor 1 (AIFM1) signaling pathway in rats with diminished ovarian reserve (DOR), so as to explore the possible mechanisms by which acupuncture improves ovarian reserve function in DOR rats.

Methods: Female SD rats were randomly divided into the control group, model group, and acupuncture group, with 6 rats in each group. The DOR model was established by one-time intraperitoneal injection of 75 mg/kg cyclophosphamide. After modeling, the acupuncture group received acupuncture at "Guanyuan" (CV4), "Zhongji" (CV3), "Qihai" (CV6), and bilateral "Sanyinjiao" (SP6), "Zigong" (EX-CA1) acupoints for 20 min each time, every other day, for a total of 15 sessions. During the experiment, the estrous cycles of the rats were observed and recorded daily. After the intervention, the body mass and ovarian mass were measured, and the ovarian index was calculated. Serum contents of estradiol (E), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) were detected by ELISA. HE staining was used to observe ovarian tissue morphology, follicle development, and ovulation. The contents of local reactive oxygen species (ROS) in ovarian tissue were measured by flow cytometry, and the protein expression levels of KEAP1, PGAM5, and AIFM1 were detected by Western blot.

Results: Compared with the control group, the model group exhibited irregular estrous cycles, increased contents of FSH and LH (<0.05), and decreased contents of E and AMH (<0.05). There was a reduction in the number of follicles at all stages and an increase in atretic follicles, with significantly elevated protein expression levels of PGAM5 and AIFM1 in ovarian tissue (<0.05). After acupuncture intervention, compared to the model group, the acupuncture group showed slight improvement in the disruption of the estrous cycle, decreased contents of FSH and LH (<0.05), increased contents of E and AMH (<0.05), an increase in the number of follicles at all stages, and a decrease in the expression level of PGAM5 in ovarian tissue (<0.05). There was no significant difference in ovanian index and ROS content in ovarian tissue among the 3 groups.

Conclusions: Acupuncture can improve ovarian reserve function, and its mechanism may be related to the inhibition of the oxeiptosis pathway.