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The Effects of Inhibin B in the Chemotherapy Drug-Induced Premature Ovarian Insufficiency Mice and hPMSCs Treatment

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Abstract

Human placenta mesenchymal stem cells (hPMSCs), have been extensively investigated on the treatment of many diseases. This study was to explore the effects of hPMSCs treatment on the chemotherapy drug-induced premature ovarian insufficiency (POI) mice. Cyclophosphamide (120 mg/kg) and busulfan (30 mg/kg) or cyclophosphamide (70 mg/kg) induced POI mice were used and hPMSCs were injected through tail vein. The hormone levels of serum, morphological changes, the expression and quantitative analysis of inhibin B (INHBB) and FSHR protein, and apoptosis of granulosa cells in ovary were detected. The granulosa cells (GCs) were detected from ovaries of mice and the different concentration of cyclophosphamide on GCs were detected by MTT assay. The apoptosis of GCs was detected by FITC Annexin V Apoptosis Detection Kit. The significant increase in FSH and decrease in E2 and INHBB were observed. Expression of human nuclei was observed in the stroma of ovaries. INHBB and FSHR levels of ovaries were reduced in the POI mice. Following hPMSCs treatment, the amounts of INHBB and FSHR significantly increased close to normal levels. The granulosa cells apoptosis increased in the POI ovaries but decreased after hPMSCs treatment. Moreover, cyclophosphamide has no effect on the GCs and no statistic difference was measured in vitro. The effects of hPMSCs treatment reduce the apoptosis of granulosa cells and restore the ovarian reserve capacity in chemotherapeutic drug–induced POI mice. The data help to further explore new potential clinical therapeutic approach for POI patients.

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Funding

This research was supported by Natural Science Foundation of Shandong Province (No. ZR2016HM77, No. ZR2016HP05) and a Project of Shandong Province Higher Educational Science and Technology Program (No. J16LK01).

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Author notes

  1. Qianqian Luo and Ranran Liu contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Sciences&Institute of Reproductive Diseases, Binzhou Medical University, Yantai, Shandong, China

    Qianqian Luo & Hongqin Zhang

  2. Department of Reproductive Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Ranran Liu

  3. Obstetrical [Maternity] Department, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Li Wang

  4. School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong, China

    Yun Hou

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  1. Qianqian Luo
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  2. Ranran Liu
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  3. Li Wang
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  4. Yun Hou
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  5. Hongqin Zhang
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Contributions

Qianqian Luo and Ranran Liu contributed equally to the work. All authors read and approved the final version of the manuscript. Qianqian Luo, Ranran Liu, and Hongqin Zhang were in charge of study design and literature research. Qianqian Luo and Li Wang performed the experiments and were in charge of manuscript preparation. Yun Hou and Qianqian Luo were responsible for revision and the final version approval of the manuscript.

Corresponding authors

Correspondence to Yun Hou or Hongqin Zhang.

Ethics declarations

The use of human placentas tissue was permitted to the Institutional Ethics Committee of Binzhou Medical University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Luo, Q., Liu, R., Wang, L. et al. The Effects of Inhibin B in the Chemotherapy Drug-Induced Premature Ovarian Insufficiency Mice and hPMSCs Treatment. Reprod. Sci. 27, 1148–1155 (2020). https://doi.org/10.1007/s43032-019-00128-y

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  • DOI: https://doi.org/10.1007/s43032-019-00128-y

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