Human Pluripotent Stem Cell-Mesenchymal Stem Cell-Derived Exosomes Promote Ovarian Granulosa Cell Proliferation and Attenuate Cell Apoptosis Induced by Cyclophosphamide in a POI-like Mouse Model

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-02, Vol.28 (5), p.2112
• Main Authors: Zhang, Lifan, Ma, Yabo, Xie, Xianguo, Du, Changzheng, Zhang, Yan, Qin, Shaogang, Xu, Jinrui, Wang, Chao, Yang, Yi, Xia, Guoliang
• Format: Article
• Language: English
• Subjects: Adult; Amenorrhea; Analysis; Animals; Apoptosis; Cancer; cell apoptosis; Cell growth; Cell Proliferation; Chemotherapy; Cyclophosphamide; Cyclophosphamide - pharmacology; Exosomes; Exosomes - metabolism; Female; Fertility; Follicles; Granulosa cells; Granulosa Cells - metabolism; Health aspects; hiMSC exosomes; Hormone replacement therapy; Hormones; Hormones, Sex; Humans; Immunofluorescence; Immunohistochemistry; Infertility; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mice; ovarian granulosa cell; Ovaries; Oxidative stress; Physiological aspects; Pluripotency; premature ovarian insufficiency; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - pathology; Primary Ovarian Insufficiency - therapy; Proteins; Reproductive status; Sex hormones; Stem cells; Western blotting
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28052112

Premature ovarian insufficiency (POI) is a complex disease which causes amenorrhea, hypergonadotropism and infertility in patients no more than 40 years old. Recently, several studies have reported that exosomes have the potential to protect ovarian function using a POI-like mouse model induced by chemotherapy drugs. In this study, the therapeutic potential of exosomes derived from human pluripotent stem cell-mesenchymal stem cells (hiMSC exosomes) was evaluated through a cyclophosphamide (CTX)-induced POI-like mouse model. POI-like pathological changes in mice were determined by serum sex-hormones levels and the available number of ovarian follicles. The expression levels of cellular proliferation proteins and apoptosis-related proteins in mouse ovarian granulosa cells were measured using immunofluorescence, immunohistochemistry and Western blotting. Notably, a positive effect on the preservation of ovarian function was evidenced, since the loss of follicles in the POI-like mouse ovaries was slowed. Additionally, hiMSC exosomes not only restored the levels of serum sex hormones, but also significantly promoted the proliferation of granulosa cells and inhibited cell apoptosis. The current study suggests that the administration of hiMSC exosomes in the ovaries can preserve female-mouse fertility.