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Protective Effects of Puerarin on Premature Ovarian Failure via Regulation of Wnt/β-catenin Signaling Pathway and Oxidative Stress

Reproductive Sciences volume 28, pages 982–990 (2021)Cite this article

Abstract

This study was designed to investigate the protective effects of puerarin (PUE), which work via the Wnt/β-catenin signaling pathway, and oxidative stress in the premature ovarian failure (POF) model. Two-month-old female mice were randomly divided into four groups. One group was used as the control, and the other three groups were injected with cyclophosphamide and busulfan to create POF models. Two POF treatment groups were gavaged with 100 or 200 mg/kg PUE for 28 days. Next, the ovaries were fixed, and the numbers of different stage follicles were measured, and the ovarian surface epithelium (OSE) was collected. Oct4 and Mvh expression, Wnt/β-catenin signaling pathway activity, the oxidative stress factors SOD2 and Nrf2, and the apoptosis-related proteins Bcl-2 and Bax were detected by IHC, RT-QPCR, and western blotting. We found that the number of follicles, Oct4 and Mvh expression, and Wnt/β-catenin-signaling activity were reduced in the POF groups (p < 0.05 or p < 0.001). After PUE treatment, the follicle number and the primordial follicle ratio increased (p < 0.01), while the atresia ratio decreased (p < 0.01). In addition, the expression levels of Oct4, Mvh, Wnt1, β-catenin, cyclin D1, SOD2, and Nrf2 showed obvious recovery compared with levels in the POF group (p < 0.01, p < 0.05, or p < 0.001). The Bcl-2/Bax ratio in the POF model had reduced by about 60% compared with the control group (p < 0.001) and improved by about 50% after PUE treatment (p < 0.001). In conclusion, PUE may improve the survival of female reproductive stem cells (FGSCs) and play a protective role against POF via a mechanism involving the Wnt/β-catenin signaling pathway, as well as relieving oxidative stress. Further investigations should focus on the culture of oocytes and FGSCs in vitro in a PUE environment with inhibitors or agonists of the Wnt signaling pathway.

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Abbreviations

POF:

premature ovarian failure

PUE:

puerarin

FGSCs:

female germline stem cells

CTX/BU:

cyclophosphamide and busulfan

Mvh:

the mouse vasa homolog

Oct-4:

octamer-4

IRI:

ischemia-reperfusion injury

FZD:

Frizzled

DshD:

disheveled

GSK3:

glycogen synthesis kinase 3

ROS:

reactive oxygen species

GSH-Px:

glutathione peroxidase

SOD:

superoxide dismutase

Nrf2:

NF-E2 p45-related factors 2

ISOs:

soy isoflavones

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Acknowledgments

This work was supported by the Project. The authors thank every member of our lab. We are grateful for the help from The Key Laboratory of Reproductive Physiology and Pathology of Jiangxi Provincial, Nanchang University.

Funding

This study was funded by the National Natural Science Foundation of China (No. 81660245 and 81771583); the Natural Science Foundation of Jiangxi Province (No. 20192BAB215009); and Program to Cultivate Major Academic and Technical Leaders of Jiangxi Province (No. 20194BCJ22005).

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Affiliations

  1. Jiangxi Medical College Nanchang University, Jiangxi Province, 330006, Nanchang, China

    Cheng Chen, Song Li, Cong Hu, Weiwei Cao, Qingfeng Fu, Jia Li, Liping Zheng & Jian Huang

  2. The Key Laboratory of Reproductive Physiology and Pathology of Jiangxi Provincial, Nanchang University, Nanchang, 330031, Jiangxi Province, China

    Jia Li, Liping Zheng & Jian Huang

Authors
  1. Cheng Chen
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  2. Song Li
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  3. Cong Hu
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  6. Jia Li
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Contributions

Cheng Chen: Conception and design, data curation, and original draft writing. Song Li and Jia Li: Investigation, collection, and assembly of data and data analysis. Cong Hu, Weiwei Cao, and Qingfeng Fu: Data collection and original draft writing. Liping Zheng: Writing-reviewing and editing. Jian Huang: Conception and design, writing-reviewing, and editing.

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Correspondence to Jian Huang.

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This study was approved by the animal ethics committee of Nanchang University.

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Chen, C., Li, S., Hu, C. et al. 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). https://doi.org/10.1007/s43032-020-00325-0

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Keywords

  • Premature ovarian failure
  • Female reproductive stem cells
  • Puerarin
  • Wnt/β-catenin pathway
  • Oxidative stress