[Exploration of the mechanism of acupuncture in the treatment of poor ovarian response based on the JAK2/STAT3 signaling pathway].

OBJECTIVES: To explore the effect of penetrative needling of "Zhibian" (BL54) to "Shuidao" (ST28) on ovarian function in mice with poor ovarian response (POR) by regulating the Janus kinase 2(JAK2)/signal transducers and activators of transcription(STAT)3 signaling pathway.

METHODS: 48 female C57BL/6 mice were randomly divided into control, model, acupuncture and inhibitor groups, with 12 mice in each group. The POR model was established by gavage of tripterygium wilfordii polyglucoside suspension (50 mg/kg). After successful modeling, the mice in the acupuncture group received penetrative needling of BL54 through ST28, with the needle retained for 20 min, once a day for 2 weeks. Mice in the inhibitor group received intraperitoneal injections of AG490 inhibitor solution (1 mg/kg) once daily for 2 weeks. On the final day of intervention, all mice underwent superovulation via intraperitoneal injection of pregnant mare serum gonadotropin (PMSG), followed by human chorionic gonadotropin (HCG) 48 h later. General conditions and estrous cycles were observed daily. Oocyte yield, ovarian wet weight, and ovarian index were measured. Serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) were assessed by ELISA. Ovarian morphology was examined via H&E staining, and ultrastructure via transmission electron microscopy. Apoptosis levels in ovarian tissue was detected by TUNEL staining. The expression levels of JAK2, STAT3, and suppressor of cytokine signaling 3 (SOCS3) mRNA were detected by PCR. Protein expression levels of JAK2, phosphorylated (p)-JAK2, STAT3, p-STAT3, SOCS3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were detected by Western blot. Immunohistochemistry was used to detect positive expression of JAK2, p-JAK2, STAT3, and p-STAT3 in ovarian tissue.

RESULTS: Compared with the control group, the rate of estrous cycle disorder, the contents of FSH and LH in serum, the rate of ovarian apoptosis, the expression of JAK2 and STAT3 mRNA, the expression of p-JAK2, p-STAT3 and Bax protein, and the positive expression of p-JAK2 and p-STAT3 in ovarian tissue were significantly increased (P<0.01);whereas the number of eggs obtained, ovarian wet weight, ovarian index, the contents of AMH and E2, the expression of SOCS3 mRNA, as well as SOCS3 and Bcl-2 protein were significantly decreased (P<0.01) in the model group. Following the intervention, the above-mentioned indexes were all reversed in the acupuncture and inhibitor groups (P<0.01, P<0.05). The ultrastructure of ovarian was damaged in the model group, which were relatively milder in the acupuncture and inhibitor groups.

CONCLUSIONS: Penetrative needling of BL54 through ST28 can improve the ovarian function in POR mice, which may be associated with its function in inhibiting the phosphorylation of the JAK2/STAT3 signaling pathway.