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Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression

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Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS.

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Data Availability

The data supporting the findings of this study are available on reasonable request from the corresponding authors.

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Funding

This work was supported by the Natural Science Foundation of China (No. 82173883, China); the Science and Technology Foundation of Xuzhou (No. KC23255, China); the administration of Traditional Chinese Medicine in Jiangsu Province (No. MS2023175, China); the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 18KA350002, China); the Provincial Commission of Health and Family Planning in Jiangsu Province (No. H2017079, China) and the Science and Technology Planning Project of Jiangsu Province (No. BE2019636, China).

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  1. Nan Zhou and Wenqiang Lv contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China

    Nan Zhou, Wenqiang Lv, Linna Chen, Kexin Chen, Qing He, Guangyan Xie, Jiachen Ma & Xueyan Zhou

  2. Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 199 South Jiefang Road, Xuzhou, 221004, China

    Yijuan Cao & Bei Zhang

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  1. Nan Zhou
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Contributions

Conceptualization: Xueyan Zhou; Methodology: Nan Zhou, Wenqiang Lv, Qing He, Jiachen Ma; Formal analysis and investigation: Wenqiang Lv, Linnan Chen, Guangyan Xie; Writing—original draft: Nan Zhou, Linnan Chen; Writing—review & editing: Xueyan Zhou, Bei Zhang; Funding Acquisition: Xueyan Zhou, Bei Zhang; Supervision: Yijuan Cao.

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Correspondence to Bei Zhang or Xueyan Zhou.

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Zhou, N., Lv, W., Chen, L. et al. Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01511-0

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