Acupuncture Reduces Apoptosis of Granulosa Cells in Rats with Premature Ovarian Failure Via Restoring the PI3K/Akt Signaling Pathway

Acupuncture is widely recognized as an effective therapy for premature ovarian failure (POF) in clinical, but information about its potential mechanisms is rarely explored. To investigate the mechanism, fifty SD female rats were randomly divided into normal group, POF group, POF+estradiol-valerate group (abbreviated as estradiol group), and POF+acupuncture group (abbreviated as acupuncture group). The estrous cycle of the rats was tracked by vaginal smears. Their ovaries morphology was observed by hematoxylin-eosin staining. The apoptotic level of granulosa cells was detected by in situ TUNEL fluorescence staining assay. Serum follicle-stimulating hormone (FSH) and estrogen (E2) levels were measured by enzyme-linked-immunosorbent-assay (ELISA). Protein and gene expression of PI3K, Akt, bcl-2, and bax were detected by Western blotting and qPCR. In the acupuncture and estradiol groups, compared with the POF group as controls, the apoptosis number of granulosa cells was significantly decreased (p < 0.05). FSH levels were decreased, while E2 levels were increased (p > 0.05). The gene and protein expression levels of PI3K, Akt, and bcl-2 were increased, while the expression levels of bax were decreased (p < 0.05), and the protein expression level of p-Akt increased. There was no significant difference between the acupuncture group and the estradiol group (p > 0.05). Acupuncture was able to regulate hormone levels in POF rats, up-regulate PI3K/Akt signaling pathway, and reduce the apoptosis of granulosa cells. This may be one of the mechanisms of acupuncture treating premature ovarian failure.

[1]  Li Huang,et al.  Acupuncture for patients with premature ovarian insufficiency , 2019, Medicine.

[2]  Sheng-feng Lu,et al.  Electro‐acupuncture attenuates the mice premature ovarian failure via mediating PI3K/AKT/mTOR pathway , 2019, Life sciences.

[3]  L. Xia,et al.  [Clinical research and the effect mechanism on premature ovarian failure treated with acupuncture in recent 20 years]. , 2018, Zhongguo zhen jiu = Chinese acupuncture & moxibustion.

[4]  Lizhen Ling,et al.  Effects and mechanism of cyclophosphamide on the ovarian structure and function of rats with premature ovarian failure , 2018 .

[5]  Yong Tang,et al.  [Involvement of PI 3 K/Akt/mTOR Signaling in Protective Effects of Moxibustion for Premature Ovarian Failure in Rats]. , 2018, Zhen ci yan jiu = Acupuncture research.

[6]  K. Jankowska Premature ovarian failure , 2014, Przeglad menopauzalny = Menopause review.

[7]  A. Pérez-Andújar,et al.  The predicted relative risk of premature ovarian failure for three radiotherapy modalities in a girl receiving craniospinal irradiation , 2013, Physics in medicine and biology.

[8]  E. Maizels,et al.  PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells , 2012, Proceedings of the National Academy of Sciences.

[9]  A. Shelling Premature ovarian failure. , 2010, Reproduction.

[10]  Kui Liu,et al.  Mechanisms maintaining the dormancy and survival of mammalian primordial follicles , 2010, Trends in Endocrinology & Metabolism.

[11]  D. Castrillon,et al.  Kit signaling via PI3K promotes ovarian follicle maturation but is dispensable for primordial follicle activation. , 2009, Developmental biology.

[12]  U. Luderer,et al.  Cyclophosphamide-induced apoptosis in COV434 human granulosa cells involves oxidative stress and glutathione depletion. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  N. Inoue,et al.  The regulation of ovarian granulosa cell death by pro- and anti-apoptotic molecules. , 2006, The Journal of reproduction and development.

[14]  P. Tsichlis,et al.  Regulation of the Akt kinase by interacting proteins , 2005, Oncogene.

[15]  Xingming Deng,et al.  Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation* , 2005, Journal of Biological Chemistry.

[16]  S. Bao,et al.  The activation of Akt/PKB signaling pathway and cell survival , 2005, Journal of cellular and molecular medicine.

[17]  B. Chakravarty,et al.  Galactose toxicity in the rat as a model for premature ovarian failure: an experimental approach readdressed. , 2003, Human reproduction.

[18]  K. Ley,et al.  Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase , 2000, Nature.

[19]  J. Annegers,et al.  Incidence of Premature Ovarian Failure , 1986, Obstetrics and gynecology.

[20]  孙丽萍,et al.  Effects of Er-Xian Decoction on Cisplatin Induced Ovarian Granulosa Cells Apoptosis Through PI3k/Akt Pathway , 2016 .

[21]  Wang Jiali,et al.  [Effects of acupuncture on PI3K/Akt/mTOR signaling pathway in rats with premature ovarian failure]. , 2015, Zhongguo zhen jiu = Chinese acupuncture & moxibustion.

[22]  Nie Ming-yu Research Progress on Regulation of the Activation of Primordial Follicles , 2014 .

[23]  Zhao Chun-li Study on Process of the Signaling Pathway of Follicle Stimulating Hormone to Promote the Ovarian Granulosa Cell Proliferation and Differentiation , 2012 .

[24]  K. Bland,et al.  Estrogen Action Via the G Protein-Coupled Receptor , GPR 30 : Stimulation of Adenylyl Cyclase and cAMP-Mediated Attenuation of the Epidermal Growth Factor Receptor-to-MAPK Signaling Axis , 2001 .