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Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer

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Abstract

Objective

To observe the effects of electroacupuncture (EA) on reproductive outcomes in women with Shen (Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer (IVF-ET), and explore the underlying molecular mechanism.

Methods

Sixty-six infertile patients with Shen deficiency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table, 33 cases in each group. Before undergoing IVF, patients in the EA and control groups received EA therapy and placebo needle puncture, respectively, for 3 menstrual cycles. Shen deficiency syndrome scores were assessed. Other outcome measures included the number of retrieved oocytes and fertilization, high-quality embryo and clinical pregnancy rates. Follicular fluid was collected on the day of oocyte retrieval, and granulosa cell expression of phosphatidylinositide 3-kinases (PI3K), serine-threonine kinase (Akt) and forkhead box O3 (Foxo3a) mRNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction.

Results

Syndrome scores for pre- versus post-treatments decreased significantly (16.53±1.75 to 8.67±1.61) in the EA group (P<0.05), but showed no significant change in the control group (17.18±1.58 to 14.74±1.58). A significant difference in score change was found between the EA and control groups (P<0.05). High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15% (195/282) vs. 60.27% (176/292) and 66.67% (22/33) vs. 42.42% (14/33), respectively, P<0.05]. The fertilization rate was equivalent in EA and control groups. No difference was found in the number of retrieved oocytes between the two groups. Granulosa cell expression levels of PI3K and Akt mRNA were significantly increased in the EA group compared with the control group, while the expression of Foxo3a was reduced (all P<0.05).

Conclusions

For infertile patients with Shen deficiency syndrome undergoing IVF, EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate. The EA-induced mechanism may involve regulation of PI3K/Akt/Foxo3a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis, possibly contributing to the improved clinical pregnancy rate (Registration No. ChiCTR 1800016217).

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References

  1. Xia JF, Inagaki Y, Zhang JF, Wang L, Song PP. Chinese medicine as complementary therapy for female infertility. Chin J Integr Med 2017;23:245–252.

    Article  PubMed  Google Scholar 

  2. Bjelica A, Nikolic S. Development and achievements of assisted reproductive technology. Med Pregled 2015;68:353–357.

    Article  Google Scholar 

  3. Zhou J, Qu F. Treating gynaecological disorders with traditional Chinese medicine: a review. Afr J Tradit Complement Alternat Med 2009;6:494–517.

    Google Scholar 

  4. Johansson J, Redman L, Veldhuis PP, Sazonova A, Labrie F, Holm G, et al. Acupuncture for ovulation induction in polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metabol 2013;304:E934–E943.

    Article  CAS  Google Scholar 

  5. Qian Y, Xia XR, Ochin H, Huang C, Gao C, Gao L, et al. Therapeutic effect of acupuncture on the outcomes of in vitro fertilization: a systematic review and meta-analysis. Arch Gynecol Obstetr 2017;295:543–558.

    Article  Google Scholar 

  6. Li J, Cui W, Sun W, Zhang QY, Guan Q. Effect of electroacupuncture on the spindle and oocytes quality in patients with PCOS. Chin J Integr Tradit West Med (Chin) 2015;35:304–309.

    Google Scholar 

  7. Jo J, Lee YJ. Effectiveness of acupuncture in women with polycystic ovarian syndrome undergoing in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis. Acupunct Med 2017;35:162–170.

    Article  PubMed  Google Scholar 

  8. Xie X, Gou W, eds. Obstetrics and gynecology. 8th ed. Beijing: People’s Medical Publishing House; 2013;369.

    Google Scholar 

  9. Munro MG, Critchley HO, Broder MS, Fraser IS, FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011;113:3–13.

    Article  PubMed  Google Scholar 

  10. Zheng XY, ed. Guidelines for Clinical Research of New Chinese herbs for Treatment of Irregular Menstruation, Amenorrhea and Infertility. 2002 ed. Beijing: China Medical Science and Technology Press; 2002:388–390.

    Google Scholar 

  11. Diagnostic and Treatment Standards for TCM Diseases. Beijing: State Administration of Traditional Chinese Medicine;1994:258–259.

  12. Tan Y, ed. Gynecology in traditional chinese medicine. 2nd ed. Beijing: China Traditional Chinese Medicine Press; 2007:324–332.

    Google Scholar 

  13. Jedel E, Labrie F, Oden A, Holm G, Nilsson L, Janson PO, et al. Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metabol 2011;300:E37–E45.

    Article  CAS  Google Scholar 

  14. Stener-Victorin E, Jedel E, Janson PO, Sverrisdottir YB. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Regul Integr Comparat Physiol 2009;297:R387–R395.

    Article  CAS  Google Scholar 

  15. Puissant F, Van Rysselberge M, Barlow P, Deweze J, Leroy F. Embryo scoring as a prognostic tool in IVF treatment. Human Reproduct 1987;2:705–708.

    Article  CAS  Google Scholar 

  16. Han JS, Ho YS. Global trends and performances of acupuncture research. Neurosc Biobehav Rev 2011;35:680–687.

    Article  Google Scholar 

  17. Qu F, Li R, Sun W, Lin G, Zhang R, Yang J, et al. Use of electroacupuncture and transcutaneous electrical acupoint stimulation in reproductive medicine: a group consensus. J Zhejiang Univ Sci B 2017;18:186–193.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Matsuda F, Inoue N, Manabe N, Ohkura S. Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells. J Reproduct Develop 2012;58:44–50.

    Article  CAS  Google Scholar 

  19. Tiwari M, Prasad S, Tripathi A, Pandey AN, Ali I, Singh AK, et al. Apoptosis in mammalian oocytes: a review. Apoptosis 2015;20:1019–1025.

    Article  CAS  PubMed  Google Scholar 

  20. Almeida CP, Ferreira MCF, Silveira CO, Campos JR, Borges IT, Baeta PG, et al. Clinical correlation of apoptosis in human granulosa cells—a review. Cell Biol Int 2018;42:1276–1281.

    Article  PubMed  Google Scholar 

  21. Uyar A, Torrealday S, Seli E. Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril 2013;99:979–997.

    Article  CAS  PubMed  Google Scholar 

  22. Brazil DP, Yang ZZ, Hemmings BA. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci 2004:29:233–242.

    Article  CAS  PubMed  Google Scholar 

  23. Liu H, Luo LL, Qian YS, Fu YC, Sui XX, Geng YJ, et al. FOXO3a is involved in the apoptosis of naked oocytes and oocytes of primordial follicles from neonatal rat ovaries. Biochem Biophys Res Commun 2009;381:722–727.

    Article  CAS  PubMed  Google Scholar 

  24. Hosaka T, Biggs WH 3rd, Tieu D, Boyer AD, Varki NM, Cavenee WK, et al. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci U S A 2004;101(9):2975–2980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Matsuda F, Inoue N, Maeda A, Cheng Y, Sai T, Gonda H, et al. Expression and function of apoptosis initiator FOXO3 in granulosa cells during follicular atresia in pig ovaries. J Reproduct Develop 2011;57:151–158.

    Article  CAS  Google Scholar 

  26. Castrillon DH, Miao L, Kollipara R, Horner JW, DePinho RA. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 2003;301:215–218.

    Article  CAS  Google Scholar 

  27. Wang XL, Wu Y, Tan LB, Tian Z, Liu JH, Zhu DS, et al. Follicle-stimulating hormone regulates pro-apoptotic protein Bcl-2-interacting mediator of cell death-extra long (BimEL)-induced porcine granulosa cell apoptosis. J Biol Chem 2012; 287;10166–10177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Stener-Victorin E, Waldenstrom U, Wikland M, Nilsson L, Hägglund L, Lundeberg T. Electro-acupuncture as a peroperative analgesic method and its effects on implantation rate and neuropeptide Y concentrations in follicular fluid. Human Reproduc 2003;18:1454–1460.

    Article  CAS  Google Scholar 

  29. Chang R, Chung PH, Rosenwaks Z. Role of acupuncture in the treatment of female infertility. Fertil Steril 2002;78:1149–1153.

    Article  PubMed  Google Scholar 

  30. Bedwell C, Dowswell T, Neilson JP, Lavender T. The use of transcutaneous electrical nerve stimulation (TENS) for pain relief in labour: a review of the evidence. Midwifery 2011;27:e141–e148.

    Article  PubMed  Google Scholar 

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Acknowledgements

We gratefully thank Prof. Hsun-Ming Chang from the University of British Columbia in Canada for revising the manuscript.

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Correspondence to Jian-wei Zhang.

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Supported by the National Natural Science Foundation of China (No. 81703958); Provincial Natural Science Foundation of Shandong Province, China (No. ZR2017PH015); Chinese Medicine Development Project of Science and Technology in Shandong province, China (No. 2017-067); State Administration of Foreign Experts Affairs, China (No. P172023018)

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Wu, Hc., Zhang, Jw., Sun, Zg. et al. Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer. Chin. J. Integr. Med. 25, 252–258 (2019). https://doi.org/10.1007/s11655-019-2948-3

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