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The role of amphiregulin in ovarian function and disease

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Abstract

Amphiregulin (AREG) is an epidermal growth factor (EGF)-like growth factor that binds exclusively to the EGF receptor (EGFR). Treatment with luteinizing hormone (LH) and/or human chorionic gonadotropin dramatically induces the expression of AREG in the granulosa cells of the preovulatory follicle. In addition, AREG is the most abundant EGFR ligand in human follicular fluid. Therefore, AREG is considered a predominant propagator that mediates LH surge-regulated ovarian functions in an autocrine and/or paracrine manner. In addition to the well-characterized stimulatory effect of LH on AREG expression, recent studies discovered that several local factors and epigenetic modifications participate in the regulation of ovarian AREG expression. Moreover, aberrant expression of AREG has recently been reported to contribute to the pathogenesis of several ovarian diseases, such as ovarian hyperstimulation syndrome, polycystic ovary syndrome, and epithelial ovarian cancer. Furthermore, increasing evidence has elucidated new applications of AREG in assisted reproductive technology. Collectively, these studies highlight the importance of AREG in female reproductive health and disease. Understanding the normal and pathological roles of AREG and elucidating the molecular and cellular mechanisms of AREG regulation of ovarian functions will inform innovative approaches for fertility regulation and the prevention and treatment of ovarian diseases. Therefore, this review summarizes the functional roles of AREG in ovarian function and disease.

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Acknowledgements

This work was supported by operating grants from the National Natural Science Foundation of China to Jung-Chien Cheng (32170868) and Lanlan Fang (32070848). This work was also supported by the International (Regional) Cooperation and Exchange Projects (81820108016) from the National Natural Science Foundation of China to Ying-Pu Sun. All figures were created with BioRender.com. We have been granted a license to use all figures in journal publications.

Funding

Funding was provided by National Natural Science Foundation of China (Grant nos. 32170868, 32070848, and 81820108016).

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  1. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 40, Daxue Road, Zhengzhou, 450052, Henan, China

    Lanlan Fang, Ying-Pu Sun & Jung-Chien Cheng

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  1. Lanlan Fang
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JCC and LF wrote the manuscript and prepared the figures and tables. YPS reviewed and provided suggestions for the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jung-Chien Cheng.

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Fang, L., Sun, YP. & Cheng, JC. The role of amphiregulin in ovarian function and disease. Cell. Mol. Life Sci. 80, 60 (2023). https://doi.org/10.1007/s00018-023-04709-8

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