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The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases

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Abstract

Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β (TGF-β) superfamily. BMP4 is a secreted protein that was originally identified due to its role in bone and cartilage development. Over the past decades, extensive literature has indicated that BMP4 and its receptors are widely expressed in the ovary. Dysregulation of BMP4 expression may play a vital role in follicular development, polycystic ovary syndrome (PCOS), and ovarian cancer. In this review, we summarized the expression pattern of BMP4 in the ovary, focused on the role of BMP4 in follicular development and steroidogenesis, and discussed the role of BMP4 in ovarian diseases such as polycystic ovary syndrome and ovarian cancer. Some studies have shown that the expression of BMP4 in the ovary is spatiotemporal and species specific, but the effects of BMP4 seem to be similar in follicular development of different species. In addition, BMP4 is involved in the development of hyperandrogenemia in PCOS and drug resistance in ovarian cancer, but further research is still needed to clarify the specific mechanisms.

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This research was funded by the National Key R&D Program of China (2018YFC1003200), the National Natural Science Foundation of China (81860276), the National Natural Science Foundation of China (11774274), and the Special Fund of Fundamental Scientific Research Business Expense for Higher School of Central Government (2042020kf0088).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Dongyong Yang, Fangfang Dai, Yanqing Wang, Min Hu & Yanxiang Cheng

  2. Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, 100044, China

    Xiao Yang

  3. School of Physics & Technology, Key Laboratory of Artificial Micro/Nano Structure of Ministry of Education, Wuhan University, Wuhan, 430072, China

    Yi Yang

Authors
  1. Dongyong Yang
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  2. Xiao Yang
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  3. Fangfang Dai
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  4. Yanqing Wang
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  5. Yi Yang
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  6. Min Hu
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  7. Yanxiang Cheng
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Contributions

Dongyong Yang, Yi Yang, Min Hu, and Yanxiang Cheng performed the PubMed search. Dongyong Yang and Xiao Yang prepared the sections on the BMP4 and BMP4 signaling pathways, the expression pattern of BMP4 in the ovary, and its role in ovarian steroidogenesis. Fangfang Dai, Yanqing Wang, and Min Hu prepared the sections on the role of BMP4 in follicular development. Yi Yang and Yanxiang Cheng prepared the sections on the role of BMP4 in reproductive diseases. Dongyong Yang and Xiao Yang organized and edited the manuscript. Dongyong Yang prepared the figures, and all authors thoroughly revised and approved the manuscript before submission.

Corresponding authors

Correspondence to Yi Yang, Min Hu or Yanxiang Cheng.

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The authors declare no competing interests.

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Dongyong Yang and Xiao Yang are joint first authors.

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Yang, D., Yang, X., Dai, F. et al. The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases. Reprod. Sci. 28, 3316–3330 (2021). https://doi.org/10.1007/s43032-021-00600-8

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