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MiRNA-99a can regulate proliferation and apoptosis of human granulosa cells via targeting IGF-1R in polycystic ovary syndrome

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

We aimed to evaluate the regulation of miR-99a to the biological functions of granulosa cells in polycystic ovary syndrome (PCOS) via targeting IGF-1R.

Methods

We collected aspirated follicular fluid in both patients with and without PCOS. Granulosa cells (GCs) were isolated through Percoll differential centrifugation to detect both miR-99a and IGF-1R expressions. We further transfected COV434 cells with miR-99a mimics to establish a miRNA-99a (miR-99a) overexpression model. We explored the regulation of miR-99a to the proliferation and apoptosis of human GCs via IGF-1R in COV434. The effect of different insulin concentrations on miR-99a expression was also evaluated.

Results

MiR-99a was significantly downregulated while IGF-1R was upregulated in patients with PCOS. MiR-99a can regulate IGF-1R on a post-transcriptional level. After transfection of miR-99a mimics, the proliferation rate was decreased and apoptosis rate was increased significantly in COV434. Exogenous insulin-like growth factor 1 (IGF-1) treatment could reverse the effect of miR-99a. MiR-99a was negatively and dose-dependently regulated by insulin in vitro.

Conclusions

MiR-99a expression was downregulated in patients with PCOS, the degree of which may be closely related to insulin resistance and hyperinsulinemia. MiR-99a could attenuate proliferation and promote apoptosis of human GCs through targeting IGF-1R, which could partly explain the abnormal folliculogenesis in PCOS.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81401268).

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Authors and Affiliations

  1. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China

    Yudi Geng, Cong Sui, Qiaohong Lai & Lei Jin

  2. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China

    Yang Xun

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  1. Yudi Geng
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  3. Yang Xun
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Geng, Y., Sui, C., Xun, Y. et al. MiRNA-99a can regulate proliferation and apoptosis of human granulosa cells via targeting IGF-1R in polycystic ovary syndrome. J Assist Reprod Genet 36, 211–221 (2019). https://doi.org/10.1007/s10815-018-1335-x

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