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miR-378d is Involved in the Regulation of Apoptosis and Autophagy of and E2 Secretion from Cultured Ovarian Granular Cells Treated by Sodium Fluoride

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Abstract

Taking excessive sodium fluoride may cause female reproductive dysfunction, but underlying molecular mechanism is unclear. The ovarian granulosa cells are the key endocrine cells releasing reproductive hormones. The miRNAs in the granulosa cells play an important function in regulating reproduction. The aim of this study is to explore the role of miRNAs in granulosa cell apoptosis and autophagy, as well as estradiol (E2) release in response to excessive sodium fluoride. The ovarian granulosa cells (KGN cells) were treated in vitro by different concentrations of sodium fluoride (NaF) for 24 h. The level of estradiol (E2) in the incubation medium was measured by ELISA kits. The total RNA and protein were collected and purified from KGN cells. The expression of miRNAs was detected by the real-time PCR. The signal molecules involved in cell apoptosis and autophagy were detected by the real-time PCR and Western blotting. Six miRNAs in granulosa cells were significantly up- or downregulated by NaF and selected for real-time PCR analysis. The miR-378d was the most significantly upregulated one dose dependently by NaF. It was positively correlated to the extent of apoptosis but negatively correlated to the level of autophagy in KGN cells in response to NaF. In addition, miR-378d promoted E2 release in response to 1 and 2 mM NaF but reduced E2 release in response to 4 and 8 mM NaF treatments. It is concluded that expression of miR-378d in ovarian granulosa cells is negatively correlated to the autophagy and E2 release and positively correlated to cell apoptosis under the influence of NaF.

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Funding

This work was funded by National Natural Science Foundation of China (grant number 81673115 and 82073496), the Huimin project of Ministry of Science and Technology of China (grant number 2012GS610101), the Department of Health of Shaanxi Province (grant number 2018D050), and the International Cooperation Foundation of Shaanxi province(2020KW-057).

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Author notes

  1. Qun Chen, Zhen Li and Zhao Xu contributed equally to this work.

Authors and Affiliations

  1. Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, 710061, People’s Republic of China

    Qun Chen

  2. Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Zhen Li

  3. School of Chemistry, Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Zhao Xu

  4. Endocrinology, School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia

    Chen Chen

  5. Guipei class 84, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China

    Jiawei Wang

  6. Kouqiang class 73, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China

    Jinyuan Zhu

  7. Shandong Shenghua Electronic New Materials Co., Ltd., Yantai, Shandong, China

    Zhaoheng Dong

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  1. Qun Chen
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Correspondence to Qun Chen.

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Chen, Q., Li, Z., Xu, Z. et al. miR-378d is Involved in the Regulation of Apoptosis and Autophagy of and E2 Secretion from Cultured Ovarian Granular Cells Treated by Sodium Fluoride. Biol Trace Elem Res 199, 4119–4128 (2021). https://doi.org/10.1007/s12011-020-02524-x

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