Acupuncture Combined with Bushen-Jianpi Decoction Ameliorates the Ovarian Function of Diminished Ovarian Reserve Rats by Regulating Phosphoinositide 3-Kinase/AKT Signaling


Cite item

Full Text

Abstract

Objective:This study aimed to explore the therapeutic efficiency as well as mechanism of acupuncture combined with Bushen-Jianpi decoction (BJD) to treat rats with diminished ovarian reserve (DOR).

Methods:A DOR rat model was constructed using zona pellucida 3 peptide, and acupuncture, BJD, and their combination were administered as therapeutic interventions. We measured changes in the ovarian indexes, the number of follicles at all levels, the serum levels of sex hormones and immune factors, the expression levels of phosphoinositide 3-kinase (PI3K), AKT, p-AKT, and caspase-3, and the changes in the proportions of splenic T cell subtypes, including T-helper 17 (Th17), Tc17, regulatory T (Treg), CD4+, and CD8+ cells.

Results:Acupuncture combined with BJD induced a decrease in the levels of follicle-stimulating and luteinizing hormones, and the effect was greater than that elicited by BJD or acupuncture alone (p < 0.05). Additionally, this combination treatment effectively abrogated the increase in the levels of interleukin-2 (IL-2), IL-17, anti-zona pellucida antibody, and cleaved caspase-3 (p < 0.05), while promoting the regulation of IL-6 and p-AKT (p < 0.01). Furthermore, treatment with acupuncture combined with BJD restored the proportions of CD4+ cells and the CD4+ / CD8+ T cell ratio (p < 0.01), decreased the proportion of CD8+ T and Th17 cells (p < 0.01), and increased the proportions of Tc17 and Treg cells (p < 0.01).

Conclusion:Combining acupuncture with BJD can enhance ovarian function in DOR rats. The regulation of sex hormone levels and immune function in rats may be attributed to the adjustment of the mRNA and proteins levels of PI3K, AKT, and caspase-3 in the PI3K/AKT signaling pathway, which leads to an improvement in the immune function of DOR rats.

About the authors

Jianting Lao

Department of Gynaecology, Shanghai Hospital of Traditional Chinese Medicine

Email: info@benthamscience.net

Panwei Hu

Department of Gynaecology, Shanghai Shuguang Hospital

Email: info@benthamscience.net

Jia Li

Department of Gynaecology, Shanghai Shuguang Hospital

Email: info@benthamscience.net

Jiahui Li

Department of Gynaecology, Shanghai Shuguang Hospital

Email: info@benthamscience.net

Xiaole Zhang

Department of Gynaecology, Shanghai Shuguang Hospital

Email: info@benthamscience.net

Hong Yang

Department of Gynaecology, Shanghai Hospital of Traditional Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

Cong Qi

Department of Gynaecology, Shanghai Shuguang Hospital

Author for correspondence.
Email: info@benthamscience.net

References

  1. Kesharwani, D.K.; Mohammad, S.; Acharya, N.; Joshi, K.S. Fertility with early reduction of ovarian reserve. Cureus, 2022, 14(10), e30326. doi: 10.7759/cureus.30326 PMID: 36407155
  2. Ata, B.; Seyhan, A.; Seli, E. Diminished ovarian reserve versus ovarian aging: overlaps and differences. Curr. Opin. Obstet. Gynecol., 2019, 31(3), 139-147. doi: 10.1097/GCO.0000000000000536 PMID: 30870184
  3. Luo, J.; Sun, Z. MicroRNAs in POI, DOR and POR. Arch. Gynecol. Obstet., 2023, 308(5), 1419-1430. doi: 10.1007/s00404-023-06922-z PMID: 36840768
  4. Park, S.U.; Walsh, L.; Berkowitz, K.M. Mechanisms of ovarian aging. Reproduction, 2021, 162(2), R19-R33. doi: 10.1530/REP-21-0022 PMID: 33999842
  5. Zhao, N.; Zhang, C.; Ding, J.; Wu, H.; Cheng, W.; Li, M.; Zhu, R.; Li, H. Altered T lymphocyte subtypes and cytokine profiles in follicular fluid associated with diminished ovary reserve. Am. J. Reprod. Immunol., 2022, 87(4), e13522. doi: 10.1111/aji.13522 PMID: 35006631
  6. Jiang, X.; Tai, H.; Xiao, X.; Zhang, S.; Cui, S.; Qi, S.; Hu, D.; Zhang, L.; Kuang, J.; Meng, X.; Li, S. Cangfudaotan decoction inhibits mitochondria-dependent apoptosis of granulosa cells in rats with polycystic ovarian syndrome. Front. Endocrinol., 2022, 13, 962154. doi: 10.3389/fendo.2022.962154 PMID: 36465612
  7. Yin, N.; Wu, C.; Qiu, J.; Zhang, Y.; Bo, L.; Xu, Y.; Shi, M.; Zhu, S.; Yang, G.; Mao, C. Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8+CD28− T cells. Stem Cell Res. Ther., 2020, 11(1), 49. doi: 10.1186/s13287-019-1537-x PMID: 32019599
  8. Han, Y.; Wang, S.; Wang, Y.; Zeng, S. IGF-1 inhibits apoptosis of porcine primary granulosa cell by targeting degradation of BimEL. Int. J. Mol. Sci., 2019, 20(21), 5356. doi: 10.3390/ijms20215356 PMID: 31661816
  9. Jiao, Y.; Zhu, S.; Li, J.; Jam Zaheer, A.; Li, M.; Huang, B. PS48 promotes in vitro maturation and developmental competence of porcine oocytes through activating PI3K/Akt signalling pathway. Reprod. Domest. Anim., 2020, 55(12), 1678-1687. doi: 10.1111/rda.13818 PMID: 32946622
  10. Artini, P.G.; Tatone, C.; Sperduti, S.; D’Aurora, M.; Franchi, S.; Di Emidio, G.; Ciriminna, R.; Vento, M.; Di Pietro, C.; Stuppia, L.; Gatta, V. Cumulus cells surrounding oocytes with high developmental competence exhibit down-regulation of phosphoinositol 1,3 kinase/protein kinase B (PI3K/AKT) signalling genes involved in proliferation and survival. Hum. Reprod., 2017, 32(12), 2474-2484. doi: 10.1093/humrep/dex320 PMID: 29087515
  11. Gong, Y.; Luo, S.; Fan, P.; Zhu, H.; Li, Y.; Huang, W. Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reprod. Biol. Endocrinol., 2020, 18(1), 121. doi: 10.1186/s12958-020-00677-x PMID: 33287836
  12. Wang, Y.; Teng, X.; Liu, J. Research progress on the effect of traditional chinese medicine on signal pathway related to premature ovarian insufficiency. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-13. doi: 10.1155/2022/7012978 PMID: 36159578
  13. Fu, Y.; Ding, D.N.; Shen, Y.; Jia, L.Y.; Yan, M.Y.; Wei, W.; Song, C.H.; Han, F.J. Complementary and alternative medicine for premature ovarian insufficiency: A review of utilization and mechanisms. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-15. doi: 10.1155/2022/9053930 PMID: 35399635
  14. Nair, A.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm., 2016, 7(2), 27-31. doi: 10.4103/0976-0105.177703 PMID: 27057123
  15. Xu, D.S.; Zhao, S.; Cui, J.J.; Ma, T.M.; Xu, B.; Yu, X.C.; Zhu, B.; Jing, X.H.; Bai, W.Z. A new attempt of re-mapping acupoint atlas in the rat. Zhen Ci Yan Jiu, 2019, 44(1), 62-65. PMID: 30773865
  16. Yin, N.; Zhao, W.; Luo, Q.; Yuan, W.; Luan, X.; Zhang, H. Restoring ovarian function with human placenta-derived mesenchymal stem cells in autoimmune-induced premature ovarian failure mice mediated by treg cells and associated cytokines. Reprod. Sci., 2018, 25(7), 1073-1082. doi: 10.1177/1933719117732156 PMID: 28954601
  17. Yin, N.; Wang, Y.; Lu, X.; Liu, R.; Zhang, L.; Zhao, W.; Yuan, W.; Luo, Q.; Wu, H.; Luan, X.; Zhang, H. Retraction note: hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway. Stem Cell Res. Ther., 2022, 13(1), 471. doi: 10.1186/s13287-022-03173-8 PMID: 36104765
  18. Li, S.; Hu, L.; Zhang, C. Effect of chronological age of patients with diminished ovarian reserve on in vitro fertilization outcome. J. Obstet. Gynaecol., 2022, 42(4), 654-657. doi: 10.1080/01443615.2021.1922996 PMID: 34384322
  19. Ke, H.; Hu, J.; Zhao, L.; Ding, L.; Jiao, X.; Qin, Y. Impact of thyroid autoimmunity on ovarian reserve, pregnancy outcomes, and offspring health in euthyroid women following in vitro fertilization/intracytoplasmic sperm injection. Thyroid, 2020, 30(4), 588-597. doi: 10.1089/thy.2018.0657 PMID: 31928166
  20. Serin, A.N.; Birge, Ö.; Uysal, A.; Görar, S.; Tekeli, F. Hashimoto’s thyroiditis worsens ovaries in polycystic ovary syndrome patients compared to Anti-Müllerian hormone levels. BMC Endocr. Disord., 2021, 21(1), 44. doi: 10.1186/s12902-021-00706-9 PMID: 33750377
  21. Deng, J.; Yang, C.; Wang, Y.; Yang, M.; Chen, H.; Ning, H.; Wang, C.; Liu, Y.; Zhang, Z.; Hu, T. Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy. Stem Cell Res. Ther., 2019, 10(1), 159. doi: 10.1186/s13287-019-1256-3 PMID: 31159888
  22. Wang, S.; Lin, S.; Zhu, M.; Li, C.; Chen, S.; Pu, L.; Lin, J.; Cao, L.; Zhang, Y. Acupuncture reduces apoptosis of granulosa cells in rats with premature ovarian failure via restoring the PI3K/Akt signaling pathway. Int. J. Mol. Sci., 2019, 20(24), 6311. doi: 10.3390/ijms20246311 PMID: 31847241
  23. Zhang, H.; Qin, F.; Liu, A.; Sun, Q.; Wang, Q.; Xie, S.; Lu, S.; Zhang, D.; Lu, Z. Electro-acupuncture attenuates the mice premature ovarian failure via mediating PI3K/AKT/mTOR pathway. Life Sci., 2019, 217, 169-175. doi: 10.1016/j.lfs.2018.11.059 PMID: 30521869
  24. Wu, H.; Zhang, J.; Sun, Z.; Xiang, S.; Qiao, Y.; Lian, F. 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., 2019, 25(4), 252-258. doi: 10.1007/s11655-019-2948-3 PMID: 31236889
  25. Liu, H.; Yang, H.; Qin, Z.; Chen, Y.; Yu, H.; Li, W.; Zhu, X.; Cai, J.; Chen, J.; Zhang, M. Exploration of the danggui buxue decoction mechanism regulating the balance of ESR and AR in the TP53-AKT signaling pathway in the prevention and treatment of POF. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-16. doi: 10.1155/2021/4862164 PMID: 35003302
  26. Dou, X.; Jin, X.; Chen, X.; Zhou, Q.; Chen, H.; Wen, M.; Chen, W. Bu-Shen-Ning-Xin decoction alleviates premature ovarian insufficiency (POI) by regulating autophagy of granule cells through activating PI3K/AKT/mTOR pathway. Gynecol. Endocrinol., 2022, 38(9), 754-764. doi: 10.1080/09513590.2022.2112941 PMID: 35989579
  27. Hu, Y.; Zhong, R.; Guo, X.; Li, G.; Zhou, J.; Yang, W.; Ren, B.; Zhu, Y. Jinfeng pills ameliorate premature ovarian insufficiency induced by cyclophosphamide in rats and correlate to modulating IL-17A/IL-6 axis and MEK/ERK signals. J. Ethnopharmacol., 2023, 307, 116242. doi: 10.1016/j.jep.2023.116242 PMID: 36775079
  28. Li, L.; Shi, X.; Shi, Y.; Wang, Z. The signaling pathways involved in ovarian follicle development. Front. Physiol., 2021, 12, 730196. doi: 10.3389/fphys.2021.730196 PMID: 34646156
  29. Maidarti, M.; Anderson, R.A.; Telfer, E.E. Crosstalk between PTEN/PI3K/Akt signalling and DNA damage in the Oocyte: Implications for primordial follicle activation, oocyte quality and ageing. Cells, 2020, 9(1), 200. doi: 10.3390/cells9010200 PMID: 31947601
  30. Qu, Q.; Liu, L.; Cui, Y.; Liu, H.; Yi, J.; Bing, W.; Liu, C.; Jiang, D.; Bi, Y. miR-126-3p containing exosomes derived from human umbilical cord mesenchymal stem cells promote angiogenesis and attenuate ovarian granulosa cell apoptosis in a preclinical rat model of premature ovarian failure. Stem Cell Res. Ther., 2022, 13(1), 352. doi: 10.1186/s13287-022-03056-y PMID: 35883161
  31. Zheng, K.; Lv, B.; Wu, L.; Wang, C.; Xu, H.; Li, X.; Wu, Z.; Zhao, Y.; Zheng, Z. Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway. Bioengineered, 2022, 13(4), 9322-9344. doi: 10.1080/21655979.2022.2052671 PMID: 35287559
  32. Esparvarinha, M.; Madadi, S.; Aslanian-Kalkhoran, L.; Nickho, H.; Dolati, S.; Pia, H.; Danaii, S.; Taghavi, S.; Yousefi, M. Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints. Cell Biol. Int., 2023, 47(3), 507-519. doi: 10.1002/cbin.11955 PMID: 36335635
  33. Gong, P.; Wang, D.; Cui, D.; Yang, Q.; Wang, P.; Yang, W.; Chen, F. Anti-aging function and molecular mechanism of radix astragali and radix astragali preparata via network pharmacology and PI3K/Akt signaling pathway. Phytomedicine, 2021, 84, 153509. doi: 10.1016/j.phymed.2021.153509 PMID: 33636579
  34. Yuan, Y.; Zhang, Y.; Zheng, R.; Yuan, H.; Zhou, R.; Jia, S.; Liu, J. Elucidating the anti-aging mechanism of Si Jun Zi Tang by integrating network pharmacology and experimental validation in vivo. Aging (Albany NY), 2022, 14(9), 3941-3955. doi: 10.18632/aging.204055 PMID: 35537009

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers