Pueratin improves diminished ovarian reserve by inhibiting apoptosis

Qi,Quan; Zhang,Xiqian; Yao,Li; Chen,Ye; Weng,Huinan

doi:10.3892/etm.2021.10858

Pueratin improves diminished ovarian reserve by inhibiting apoptosis

Authors:
- Quan Qi
- Xiqian Zhang
- Li Yao
- Ye Chen
- Huinan Weng
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Affiliations: Reproductive Medicine Center, Guangdong Women and Children Hospital, Guangdong, Guangzhou 511442, P.R. China
Published online on: October 11, 2021 https://doi.org/10.3892/etm.2021.10858
Article Number: 1423
Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pueratin (Pue) is an extract from Pueraria lobata, and exhibits therapeutic effects for the treatment of inflammation. However, the beneficial effects and mechanisms underlying Pue in the treatment of diminished ovarian reserve (DOR) remains to be fully elucidated. The aim of the present study was to investigate the effect of Pue on Bcl‑2 and Bax protein expression in rats with DOR, associated with infertility within clinical practice, induced by 4‑vinylcyclohexene diepoxide (VCD). A model of DOR was established in female Sprague Dawley rats by an intraperitoneal injection of 80 mg/kg VCD daily for 45 days. From day 1, the Sprague Dawley rats were orally administered with drugs daily for 45 days. They were divided into normal, model, Pue‑low dose (L), Pue‑medium dose (M) and Pue‑high dose (H) groups (50, 100 and 300 mg/kg Pue, respectively). Follicle‑stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels were subsequently detected using ELISA. H&E staining and TUNEL staining were used to evaluate histopathological changes and apoptosis levels in the ovary, respectively. Bcl‑2 and Bax protein expression levels in rat ovaries were evaluated using immunohistochemistry and western blotting. Compared with those in the model group, FSH and LH levels in the Pue‑L, ‑M and ‑H groups were significantly decreased, whilst E2 levels were significantly increased (P<0.05). After intragastric administration, the volume of the ovaries and uteri of rats in the Pue groups was increased compared with the model group, and the numbers of primordial follicles and primary follicles were also increased. The number of apoptotic cells and the expression of Bax were significantly reduced in a dose‑dependent manner (P<0.05), compared with the model group. In addition, Bcl‑2 protein expression and the Bcl‑2/Bax ratio were found to be significantly increased in the Pue‑treated groups in a dose‑dependent manner (P<0.05), compared with the model group. In conclusion, Pue treatment improved ovarian function by regulating hormone balance in addition to Bcl‑2 and Bax expression.

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1	Jaillard S, Sreenivasan R, Beaumont M, Robevska G, Dubourg C, Knarston IM, Akloul L, van den Bergen J, Odent S, Croft B, et al: Analysis of NR5A1 in 142 patients with premature ovarian insufficiency, diminished ovarian reserve, or unexplained infertility. Maturitas. 131:78–86. 2020.PubMed/NCBI View Article : Google Scholar
2	Tanaka Y, Hsueh AJ and Kawamura K: Surgical approaches of drug-free in vitro activation and laparoscopic ovarian incision to treat patients with ovarian infertility. Fertil Steril. 114:1355–1357. 2020.PubMed/NCBI View Article : Google Scholar
3	Kawamura K, Kawamura N and Hsueh AJ: Activation of dormant follicles: A new treatment for premature ovarian failure? Curr Opin Obstet Gynecol. 28:217–222. 2016.PubMed/NCBI View Article : Google Scholar
4	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
5	Quaas AM and Legro RS: Pharmacology of medications used for ovarian stimulation. Best Pract Res Clin Endocrinol Metab. 33:21–33. 2019.PubMed/NCBI View Article : Google Scholar
6	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
7	Chen C, Li S, Hu C, Cao W, Fu Q, Li J, Zheng L and Huang J: Protective Effects of Puerarin on Premature Ovarian Failure via Regulation of Wnt/β-catenin Signaling Pathway and Oxidative Stress. Reprod Sci. 28:982–990. 2021.PubMed/NCBI View Article : Google Scholar
8	Chlebowski RT, Manson JE, Anderson GL, Cauley JA, Aragaki AK, Stefanick ML, Lane DS, Johnson KC, Wactawski-Wende J, Chen C, et al: Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. J Natl Cancer Inst. 105:526–535. 2013.PubMed/NCBI View Article : Google Scholar
9	Worsley R, Davis SR, Gavrilidis E, Gibbs Z, Lee S, Burger H and Kulkarni J: Hormonal therapies for new onset and relapsed depression during perimenopause. Maturitas. 73:127–133. 2012.PubMed/NCBI View Article : Google Scholar
10	Zhou YX, Zhang H and Peng C: Puerarin: A review of pharmacological effects. Phytother Res. 28:961–975. 2014.PubMed/NCBI View Article : Google Scholar
11	Jiang M, Yun Q, Niu G, Gao Y, Shi F and Yu S: Puerarin prevents inflammation and apoptosis in the neurocytes of a murine Parkinson's disease model. Genet Mol Res: Oct 5, 2016 (Epub ahead of print). doi: 10.4238/gmr.15047501.
12	Zhou X, Bai C, Sun X, Gong X, Yang Y, Chen C, Shan G and Yao Q: Puerarin attenuates renal fibrosis by reducing oxidative stress induced-epithelial cell apoptosis via MAPK signal pathways in vivo and in vitro. Ren Fail. 39:423–431. 2017.PubMed/NCBI View Article : Google Scholar
13	Xue Q, Liu Y, He R, Yang S, Tong J, Li X, Chen Y and Xu X: Lyophilized Powder of Catalpol and Puerarin Protects Neurovascular Unit from Stroke. Int J Biol Sci. 12:367–380. 2016.PubMed/NCBI View Article : Google Scholar
14	Ma Y, Gai Y, Yan J, Li J and Zhang Y: Puerarin Attenuates Anoxia/Reoxygenation Injury Through Enhancing Bcl-2 Associated Athanogene 3 Expression, a Modulator of Apoptosis and Autophagy. Med Sci Monit. 22:977–983. 2016.PubMed/NCBI View Article : Google Scholar
15	Gaumer S, Guénal I, Brun S, Théodore L and Mignotte B: Bcl-2 and Bax mammalian regulators of apoptosis are functional in Drosophila. Cell Death Differ. 7:804–814. 2000.PubMed/NCBI View Article : Google Scholar
16	Lin H, Zhang XM, Chen C and Chen BD: Apoptosis of Mo7e leukemia cells is associated with the cleavage of Bcl-2 into a shortened fragment that is not functional for heterodimerization with Bcl-2 and Bax. Exp Cell Res. 261:180–186. 2000.PubMed/NCBI View Article : Google Scholar
17	Li L, Dong J, Yan L, Yong J, Liu X, Hu Y, Fan X, Wu X, Guo H, Wang X, et al: Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions. Cell Stem Cell. 20:858–873.e4. 2017.PubMed/NCBI View Article : Google Scholar
18	Xu M, Che L, Yang Z, Zhang P, Shi J, Li J, Lin Y, Fang Z, Che L, Feng B, et al: Proteomic Analysis of Fetal Ovaries Reveals That Primordial Follicle Formation and Transition Are Differentially Regulated. BioMed Res Int. 2017(6972030)2017.PubMed/NCBI View Article : Google Scholar
19	Birt JA, Taylor KH, Davis JW and Sharpe-Timms KL: Developmental exposure of fetal ovaries and fetal germ cells to endometriosis in an endometriosis model causes differential gene expression in the preimplantation embryos of the first-generation and second-generation embryos. Fertil Steril. 100:1436–1443. 2013.PubMed/NCBI View Article : Google Scholar
20	Liu H, Zhang X, Zhong X, Li Z, Cai S, Yang P, Ou C and Chen M: Puerarin inhibits vascular calcification of uremic rats. Eur J Pharmacol. 855:235–243. 2019.PubMed/NCBI View Article : Google Scholar
21	Lei L, Zhang H, Jin S, Wang F, Fu M, Wang H and Xia G: Stage-specific germ-somatic cell interaction directs the primordial folliculogenesis in mouse fetal ovaries. J Cell Physiol. 208:640–647. 2006.PubMed/NCBI View Article : Google Scholar
22	Juneja SC, Barr KJ, Enders GC and Kidder GM: Defects in the germ line and gonads of mice lacking connexin43. Biol Reprod. 60:1263–1270. 1999.PubMed/NCBI View Article : Google Scholar
23	Pepling ME: From primordial germ cell to primordial follicle: Mammalian female germ cell development. Genesis. 44:622–632. 2006.PubMed/NCBI View Article : Google Scholar
24	Vaskivuo TE and Tapanainen JS: Apoptosis in the human ovary. Reprod Biomed Online. 6:24–35. 2003.PubMed/NCBI View Article : Google Scholar
25	Perez GI, Maravei DV, Trbovich AM, Cidlowski JA, Tilly JL and Hughes FM Jr: Identification of potassium-dependent and -independent components of the apoptotic machinery in mouse ovarian germ cells and granulosa cells. Biol Reprod. 63:1358–1369. 2000.PubMed/NCBI View Article : Google Scholar
26	Wang S, Sun M, Yu L, Wang Y, Yao Y and Wang D: Niacin Inhibits Apoptosis and Rescues Premature Ovarian Failure. Cell Physiol Biochem. 50:2060–2070. 2018.PubMed/NCBI View Article : Google Scholar
27	Silva JRV, Lima FEO, Souza ALP and Silva AWB: Interleukin-1β and TNF-α systems in ovarian follicles and their roles during follicular development, oocyte maturation and ovulation. Zygote. 28:270–277. 2020.PubMed/NCBI View Article : Google Scholar
28	Wang S, Lin S, Zhu M, Li C, Chen S, Pu L, Lin J, Cao L and 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. 20(E6311)2019.PubMed/NCBI View Article : Google Scholar
29	Kappeler CJ and Hoyer PB: 4-vinylcyclohexene diepoxide: A model chemical for ovotoxicity. Syst Biol Reprod Med. 58:57–62. 2012.PubMed/NCBI View Article : Google Scholar
30	Chauhan P, Sodhi A and Tarang S: Cisplatin-treated murine peritoneal macrophages induce apoptosis in L929 cells: Role of Fas-Fas ligand and tumor necrosis factor-tumor necrosis factor receptor 1. Anticancer Drugs. 18:187–196. 2007.PubMed/NCBI View Article : Google Scholar
31	Almarzoug MHA, Ali D, Alarifi S, Alkahtani S and Alhadheq AM: Platinum nanoparticles induced genotoxicity and apoptotic activity in human normal and cancer hepatic cells via oxidative stress-mediated Bax/Bcl-2 and caspase-3 expression. Environ Toxicol. 35:930–941. 2020.PubMed/NCBI View Article : Google Scholar
32	Roosa KA, Mukai M and Place NJ: 4-Vinylcyclohexene diepoxide reduces fertility in female Siberian hamsters when treated during their reproductively active and quiescent states. Reprod Toxicol. 51:40–46. 2015.PubMed/NCBI View Article : Google Scholar
33	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007.PubMed/NCBI View Article : Google Scholar
34	Luciano AM, Modina S, Gandolfi F, Lauria A and Armstrong DT: Effect of cell-to-cell contact on in vitro deoxyribonucleic acid synthesis and apoptosis responses of bovine granulosa cells to insulin-like growth factor-I and epidermal growth factor. Biol Reprod. 63:1580–1585. 2000.PubMed/NCBI View Article : Google Scholar
35	Gosden RG and Faddy MJ: Biological bases of premature ovarian failure. Reprod Fertil Dev. 10:73–78. 1998.PubMed/NCBI View Article : Google Scholar
36	Klein JL, Adams SM, De Moura AF, Alves Filho DC, Maidana FM, Brondani IL, Cocco JM, Rodrigues LDS, Pizzuti LAD and Da Silva MB: Productive performance of beef cows subjected to different nutritional levels in the third trimester of gestation. Animal. 15(100089)2021.PubMed/NCBI View Article : Google Scholar
37	Wang H, Jiao H, Jiang Z and Chen R: Propofol inhibits migration and induces apoptosis of pancreatic cancer PANC-1 cells through miR-34a-mediated E-cadherin and LOC285194 signals. Bioengineered. 11:510–521. 2020.PubMed/NCBI View Article : Google Scholar
38	Erfani S, Moghimi A, Aboutaleb N and Khaksari M: Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression. Basic Clin Neurosci. 10:451–459. 2019.PubMed/NCBI View Article : Google Scholar
39	Fakhrabadi HG, Rabbani-Chadegani A, Ghadam P and Amiri S: Protective effect of bleomycin on 5-azacitidine induced cytotoxicity and apoptosis in mice hematopoietic stem cells via Bcl-2/Bax and HMGB1 signaling pathway. Toxicol Appl Pharmacol. 396(114996)2020.PubMed/NCBI View Article : Google Scholar