Moxibustion improves ovarian function based on the regulation of the androgen balance Corrigendum in /10.3892/etm.2022.11113

Jin,Xun; Cheng,Jie; Shen,Jie; Lv,Xing; Li,Qian; Mu,Yanyun; Bai,Hua; Liu,Yan; Xia,Youbing

doi:10.3892/etm.2021.10664

Moxibustion improves ovarian function based on the regulation of the androgen balance

Corrigendum in: /10.3892/etm.2022.11113

Authors:
- Xun Jin
- Jie Cheng
- Jie Shen
- Xing Lv
- Qian Li
- Yanyun Mu
- Hua Bai
- Yan Liu
- Youbing Xia
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Affiliations: College of Acupuncture and Massage, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China, Central Research Institute of Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 200020, P.R. China, Traditional Chinese Medicine Department, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China
Published online on: August 30, 2021 https://doi.org/10.3892/etm.2021.10664
Article Number: 1230
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The effect of androgens on follicular development and female reproduction has become an active research topic. Moxibustion is a Traditional Chinese Medicine therapy that has been reported to be able to prevent and treat numerous ovary‑related problems. However, studies on the effect of moxibustion for diminished ovarian reserve (DOR) on androgen balance are still lacking. The present study aimed to assess the efficacy of moxibustion intervention prior to disease onset and at the early stage of disease in a rat model of DOR and explore the mechanisms of its effect on ovarian function. A total of 32 rats were randomly divided into four groups: Blank group, Model group (a drug‑induced model of DOR), Moxibustion group 1 and Moxibustion group 2. Moxibustion was performed on the BL23 and RN4 acupoints of female rats daily for a total of 20 days (once a day, five times a week for a total of 4 weeks). The two moxibustion groups were established with different intervention times: One group was subjected to pre‑disease intervention and the other group to early‑disease intervention. The ovarian function was evaluated by detecting anti‑Mullerian hormone (AMH), follicle‑stimulating hormone (FSH), estradiol (E2), testosterone (T), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and androgen receptor (AR) levels in the serum or the ovary samples. To further investigate the downstream regulatory factors for AR after moxibustion treatment for pre‑disease or early‑disease intervention, FSH receptor (FSHR) and microRNA (miR)‑125b expression in ovaries were also analyzed. The results indicated that AMH and DHT levels were reduced in the model group compared with those in the blank group, while FSH, T and DHEA levels were increased. AMH and DHT levels were increased in Moxibustion group 1 compared with those in the model group, while FSH, T and DHEA levels were reduced. There was no difference in E2 levels between Moxibustion group 1 and the model group. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 1. There was no difference in FSHR mRNA in the ovaries between Moxibustion group 1 and the model group. miR‑125b levels were significantly increased in Moxibustion group 1 as compared with those in the model group. Furthermore, AMH and DHT levels were increased in Moxibustion group 2 compared with those in the model group, while FSH, T and DHEA levels were reduced. E2 levels were significantly decreased in Moxibustion group 2 compared with those in the model group. The relative mRNA expression of AR, FSHR and miR‑125b was decreased following establishment of the model. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 2. In comparison with the blank and model groups, the FSHR content in the ovary of Moxibustion group 2 was significantly increased. miR‑125b levels were not obviously altered in Moxibustion group 2 as compared with those in the model group. In addition, there was no significant difference in AMH, FSH, T and DHEA levels between the two moxibustion groups. E2 and DHT levels were higher in Moxibustion group 1 than in Moxibustion group 2. There was no difference in AR mRNA expression between the two moxibustion groups. FSHR mRNA levels were lower in Moxibustion group 1 than in Moxibustion group 2, while miR‑125b mRNA levels were higher in Moxibustion group 1 than in Moxibustion group 2. In conclusion, the present study suggested that moxibustion intervention prior to disease onset and at the early disease stage was able to improve ovarian function via modulation of the AR‑mediated stable equilibrium of androgens. However, the effects and mechanisms of moxibustion intervention for pre‑disease and early‑disease intervention of DOR appear to be different. The appropriate duration of treatment and the time‑effect relationship require to be further studied.

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1	Devine K, Mumford SL, Wu M, DeCherney AH, Hill MJ and Propst A: Diminished ovarian reserve in the United States assisted reproductive technology population: Diagnostic trends among 181,536 cycles from the Society for assisted reproductive technology clinic outcomes reporting system. Fertil Steril. 104:612–619.e3. 2015.PubMed/NCBI View Article : Google Scholar
2	Greene AD, Patounakis G and Segars JH: Genetic associations with diminished ovarian reserve: A systematic review of the literature. J Assist Reprod Genet. 31:935–946. 2014.PubMed/NCBI View Article : Google Scholar
3	Zhao M, Feng F, Chu C, Yue W and Li L: A novel EIF4ENIF1 mutation associated with a diminished ovarian reserve and premature ovarian insufficiency identified by whole-exome sequencing. J Ovarian Res. 12(119)2019.PubMed/NCBI View Article : Google Scholar
4	Gleicher N, Kim A, Weghofer A, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ and Barad DH: Hypoandrogenism in association with diminished functional ovarian reserve. Hum Reprod. 28:1084–1091. 2013.PubMed/NCBI View Article : Google Scholar
5	Vodo S, Bechi N, Petroni A, Muscoli C and Aloisi AM: Testosterone-induced effects on lipids and inflammation. Mediators Inflamm. 2013(183041)2013.PubMed/NCBI View Article : Google Scholar
6	Sen A, Prizant H, Light A, Biswas A, Hayes E, Lee HJ, Barad D, Gleicher N and Hammes SR: Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Proc Natl Acad Sci USA. 111:3008–3013. 2014.PubMed/NCBI View Article : Google Scholar
7	Prizant H, Gleicher N and Sen A: Androgen actions in the ovary: Balance is key. J Endocrinol. 222:R141–R151. 2014.PubMed/NCBI View Article : Google Scholar
8	Shi XL, Zhao C, Yang S, Hu XY and Liu SM: Moxibustion reduces ovarian granulosa cell apoptosis associated with perimenopause in a natural aging rat model. Evid Based Complement Alternat Med. 2015(742914)2015.PubMed/NCBI View Article : Google Scholar
9	Zhang CR, Deng JL, Zhu WN, Miao MX, Shen WW, Cao SJ and Tang Y: Involvement of PI 3 K/Akt/mTOR signaling in protective effects of moxibustion for premature ovarian failure in rats. Zhen Ci Yan Jiu. 43:75–79. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese).
10	Wu S and Yan J: Clinical observation on premature ovarian failure by warming acupuncture at Zusanli (ST 36) and Guanyuan (CV 4) combined with ginger moxibustion at Baliao points. Zhongguo Zhen Jiu. 38:1267–1271. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese).
11	Zhu S, Wang Y, Chang X, Chen H and Jin X: The protective effect of pre-moxibustion on reproductive hormones profile of rats with tripterygium glycosides-induced ovarian damage. Complement Med Res. 27:401–409. 2020.PubMed/NCBI View Article : Google Scholar
12	Shen J, Shen M, Li Z, Zhang R, Li X and Ai B: Effects of moxibustion at Shenshu (BL 23) on level of sex hormones and AMH in sub-health peri-menopausal women. Zhongguo Zhen Jiu. 37:381–385. 2017.PubMed/NCBI View Article : Google Scholar : (In Chinese).
13	Yang X, Wang W, Zhang Y, Wang J and Huang F: Moxibustion improves ovary function by suppressing apoptosis events and upregulating antioxidant defenses in natural aging ovary. Life Sci. 229:166–172. 2019.PubMed/NCBI View Article : Google Scholar
14	Zhang Y, Yu B, Chen J, Zhao Z, Wang Jiali, Huang F, Lin Y, Wang M, Zhang Y and Wei B: Effects of acupuncture on PI3K/Akt/mTOR signaling pathway in rats with premature ovarian failure. Zhongguo Zhen Jiu. 35:53–58. 2015.PubMed/NCBI(In Chinese).
15	Xia L and Xia Y: Clinical research and the effect mechanism on premature ovarian failure treated with acupuncture in recent 20 years. Zhongguo Zhen Jiu. 38:5653–5670. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese).
16	Zhou XL, Xu JJ, Ni YH, Chen XC, Zhang HX, Zhang XM, Liu WJ, Luo LL and Fu YC: SIRT1 activator (SRT1720) improves the follicle reserve and prolongs the ovarian lifespan of diet-induced obesity in female mice via activating SIRT1 and suppressing mTOR signaling. J Ovarian Res. 7(97)2014.PubMed/NCBI View Article : Google Scholar
17	Ma M, Chen XY, Gu C, Xiao XR, Guo T and Li B: Biochemical changes of oxidative stress in premature ovarian insufficiency induced by tripterygium glycosides. Int J Clin Exp Pathol. 7:8855–8861. 2014.PubMed/NCBI
18	Zhang T, Yan D, Yang Y, Ma A, Li L, Wang Z, Pan Q and Sun Z: The comparison of animal models for premature ovarian failure established by several different source of inducers. Regul Toxicol Pharmacol. 81:223–232. 2016.PubMed/NCBI View Article : Google Scholar
19	Guo Y and Fang JQ: Experimental acupuncture. Beijing: China Traditional Medicine Press, pp402-407, 2012.
20	Machholz E, Mulder G, Ruiz C, Corning BF and Pritchett-Corning KR: Manual restraint and common compound administration routes in mice and rats. J Vis Exp. (2771)2012.PubMed/NCBI View Article : Google Scholar
21	Buerge T and Weiss T: The laboratory mouse: Handling and restraint. Elsevier, pp517-526, 2004.
22	Morton DB and Griffiths PH: Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment. Vet Rec. 116:431–436. 1985.PubMed/NCBI View Article : Google Scholar
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
24	Wang Q, Lu G, Xie Z, Xie ZJ, Li HX and Shen MH: Effect of moxibustion on Nrf2/HO-1 signaling pathway in rats with diminished ovarian reserve. Zhongguo Zhen Jiu. 41:53–58. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).
25	Li X and Xu CJ: Diseases of the female reproductive system 1nd edition. Beijing: People's Medical Publishing House, pp1-4, 2015.
26	Galey-Fontaine J, Cédrin-Durnerin I, Chaïbi R, Massin N and Hugues JN: Age and ovarian reserve are distinct predictive factors of cycle outcome in low responders. Reprod Biomed Online. 10:94–99. 2005.PubMed/NCBI View Article : Google Scholar
27	Shatavi SV, Llanes B and Luborsky JL: Association of unexplained infertility with gonadotropin and ovarian antibodies. Am J Reprod Immunol. 56:286–291. 2006.PubMed/NCBI View Article : Google Scholar
28	Cohen J, Chabbert-Buffet N and Darai E: Diminished ovarian reserve, premature ovarian failure, poor ovarian responder-a plea for universal definitions. J Assist Reprod Genet. 32:1709–1712. 2015.PubMed/NCBI View Article : Google Scholar
29	Li HF and Tan Y: Discussion on the prevention and treatment of ovarian reserve function decline from the idea of treating pre-disease. J Tradit Chin Med. 31:155–157. 2016.
30	Huang XC, Cao XC and Wang XY: Evaluation and revision of TCM guidelines on premature ovarian failure. Henan Tradit Chin Med. 39:82–86. 2019.
31	Liao HH, Zhao Y and Shi Y: ZHANG Yu-zhen's ideas and approaches concerning treatment of premature ovarian failure. Glob Tradit Chin Med. 8:780–782. 2015.
32	Meng JC and Wang XH: Internal classic. Plain questions 1nd edition. Shanghai: Shanghai Science and Technology Press, pp12-20, 2019.
33	Xu H, Zeng L, Yang R, Feng Y, Li R and Qiao J: Retrospective cohort study: AMH is the best ovarian reserve markers in predicting ovarian response but has unfavorable value in predicting clinical pregnancy in GnRH antagonist protocol. Arch Gynecol Obstet. 295:763–770. 2017.PubMed/NCBI View Article : Google Scholar
34	Zebitay AG, Cetin O, Verit FF, Keskin S, Sakar MN, Karahuseyinoglu S, Ilhan G and Sahmay S: The role of ovarian reserve markers in prediction of clinical pregnancy. J Obstet Gynaecol. 37:492–497. 2017.PubMed/NCBI View Article : Google Scholar
35	Du EQ, Gao X and Shang L: Assessments of anti-mullerian hormone combining with FSH and FSH/LH in the advanced maternal women during the reproductive year with ovarian reserve. Med J West China. 30:701–703. 2018.
36	Zhang H, Luo Q, Lu X, Yin N, Zhou D, Zhang L, Zhao W, Wang D, Du P, Hou Y, et al: Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice. Stem Cell Res Ther. 9(20)2018.PubMed/NCBI View Article : Google Scholar
37	Lunding SA, Aksglaede L, Anderson RA, Main KM, Juul A, Hagen CP and Pedersen AT: AMH as predictor of premature ovarian insufficiency: A longitudinal study of 120 turner syndrome patients. J Clin Endocrinol Metab. 100:E1030–E1038. 2015.PubMed/NCBI View Article : Google Scholar
38	Song JM: Women testosterone levels and ovarian reserve evaluation index and the correlation of IVF outcome studies. Kunming: Kunming Medical University, pp26-27, 2016.
39	Walters KA and Handelsman DJ: Role of androgens in the ovary. Mol Cell Endocrinol. 465:36–47. 2018.PubMed/NCBI View Article : Google Scholar
40	Gleicher N, Weghofer A, Lee IH and Barad DH: FMR1 genotype with autoimmunity-associated polycystic ovary-like phenotype and decreased pregnancy chance. PLoS One. 5(e15303)2010.PubMed/NCBI View Article : Google Scholar
41	Qin JC, Fan L and Qin AP: The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis. J Gynecol Obstet Hum Reprod. 46:1–7. 2017.PubMed/NCBI View Article : Google Scholar
42	Burger HG: Androgen production in women. Fertil Steril. 77 (Suppl 4):S3–S5. 2002.PubMed/NCBI View Article : Google Scholar
43	Labrie F and Labrie C: DHEA and intracrinology at menopause, a positive choice for evolution of the human species. Climacteric. 16:205–213. 2013.PubMed/NCBI View Article : Google Scholar
44	Gleicher N and Barad DH: Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol. 9(67)2011.PubMed/NCBI View Article : Google Scholar
45	Walters KA, Allan CM, Jimenez M, Lim PR, Davey RA, Zajac JD, Illingworth P and Handelsman DJ: Female mice haploinsufficient for an inactivated androgen receptor (AR) exhibit age-dependent defects that resemble the AR null phenotype of dysfunctional late follicle development, ovulation, and fertility. Endocrinology. 148:3674–3684. 2007.PubMed/NCBI View Article : Google Scholar
46	Walters KA, Middleton LJ, Joseph SR, Hazra R, Jimenez M, Simanainen U, Allan CM and Handelsman DJ: Targeted loss of androgen receptor signaling in murine granulosa cells of preantral and antral follicles causes female subfertility. Biol Reprod. 87(151)2012.PubMed/NCBI View Article : Google Scholar
47	Zhu B: The plasticity of acupoint. Zhongguo Zhen Jiu. 35:1203–1208. 2015.PubMed/NCBI(In Chinese).
48	Xu B and Han X: Discussion on primordial and sensitized states of acupuncture points. Zhen Ci Yan Jiu. 43:273–276. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese).
49	Zhu H, Nan S, Suo C, Zhang Q, Hu M, Chen R, Wan J, Li M, Chen J and Ding M: Electro-acupuncture affects the activity of the hypothalamic-pituitary-ovary axis in female rats. Front Physiol. 10(466)2019.PubMed/NCBI View Article : Google Scholar