{"title":"人脐带间充质干细胞来源的细胞外囊泡通过PI3K/Akt级联对卵巢早衰小鼠卵巢功能的治疗作用","authors":"Nan Li, Xue Fan, Lihong Liu, Yanbing Liu","doi":"10.4081/ejh.2023.3506","DOIUrl":null,"url":null,"abstract":"<p><p>Premature ovarian failure (POF) mainly refers to ovarian dysfunction in females younger than forty. Mesenchymal stem cells (MSCs) are considered an increasingly promising therapy for POF. This study intended to uncover the therapeutic effects of human umbilical cord MSC-derived extracellular vesicles (hucMSCEVs) on POF. hucMSCs were identified by observing morphology and examining differentiation capabilities. EVs were extracted from hucMSCs and later identified utilizing nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. POF mouse models were established by injecting D-galactose (Dgal). The estrous cycles were assessed through vaginal cytology, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), estradiol (E2), and progesterone (P) were measured by ELISA. The human ovarian granulosa cell line KGN was used for in vitro experiments. The uptake of hucMSC-EVs by KGN cells was detected. After D-gal treatment, cell proliferation and apoptosis were assessed via CCK-8 assay and flow cytometry. The PI3K/Akt pathway-related proteins were determined by Western blotting. Our results revealed that POF mice had prolonged estrous cycles, increased FSH and LH levels, and decreased AMH, E2, and P levels. Treatment with hucMSC-EVs partially counteracted the above changes. D-gal treatment reduced proliferation and raised apoptosis in KGN cells, while hucMSC-EV treatment annulled the changes. D-gal-treated cells exhibited downregulated p-PI3K/PI3K and p-Akt/Akt levels, while hucMSC-EVs activated the PI3K/Akt pathway. LY294002 suppressed the roles of hucMSC-EVs in promoting KGN cell proliferation and lowering apoptosis. Collectively, hucMSC-EVs facilitate proliferation and suppress apoptosis of ovarian granulosa cells by activating the PI3K/Akt pathway, thereby alleviating POF.</p>","PeriodicalId":50487,"journal":{"name":"European Journal of Histochemistry","volume":"67 3","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/ce/ejh-67-3-3506.PMC10476539.pdf","citationCount":"0","resultStr":"{\"title\":\"Therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on ovarian functions through the PI3K/Akt cascade in mice with premature ovarian failure.\",\"authors\":\"Nan Li, Xue Fan, Lihong Liu, Yanbing Liu\",\"doi\":\"10.4081/ejh.2023.3506\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Premature ovarian failure (POF) mainly refers to ovarian dysfunction in females younger than forty. Mesenchymal stem cells (MSCs) are considered an increasingly promising therapy for POF. This study intended to uncover the therapeutic effects of human umbilical cord MSC-derived extracellular vesicles (hucMSCEVs) on POF. hucMSCs were identified by observing morphology and examining differentiation capabilities. EVs were extracted from hucMSCs and later identified utilizing nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. POF mouse models were established by injecting D-galactose (Dgal). The estrous cycles were assessed through vaginal cytology, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), estradiol (E2), and progesterone (P) were measured by ELISA. The human ovarian granulosa cell line KGN was used for in vitro experiments. The uptake of hucMSC-EVs by KGN cells was detected. After D-gal treatment, cell proliferation and apoptosis were assessed via CCK-8 assay and flow cytometry. The PI3K/Akt pathway-related proteins were determined by Western blotting. Our results revealed that POF mice had prolonged estrous cycles, increased FSH and LH levels, and decreased AMH, E2, and P levels. Treatment with hucMSC-EVs partially counteracted the above changes. D-gal treatment reduced proliferation and raised apoptosis in KGN cells, while hucMSC-EV treatment annulled the changes. D-gal-treated cells exhibited downregulated p-PI3K/PI3K and p-Akt/Akt levels, while hucMSC-EVs activated the PI3K/Akt pathway. LY294002 suppressed the roles of hucMSC-EVs in promoting KGN cell proliferation and lowering apoptosis. Collectively, hucMSC-EVs facilitate proliferation and suppress apoptosis of ovarian granulosa cells by activating the PI3K/Akt pathway, thereby alleviating POF.</p>\",\"PeriodicalId\":50487,\"journal\":{\"name\":\"European Journal of Histochemistry\",\"volume\":\"67 3\",\"pages\":\"\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-07-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/ce/ejh-67-3-3506.PMC10476539.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Histochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.4081/ejh.2023.3506\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Histochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.4081/ejh.2023.3506","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on ovarian functions through the PI3K/Akt cascade in mice with premature ovarian failure.
Premature ovarian failure (POF) mainly refers to ovarian dysfunction in females younger than forty. Mesenchymal stem cells (MSCs) are considered an increasingly promising therapy for POF. This study intended to uncover the therapeutic effects of human umbilical cord MSC-derived extracellular vesicles (hucMSCEVs) on POF. hucMSCs were identified by observing morphology and examining differentiation capabilities. EVs were extracted from hucMSCs and later identified utilizing nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. POF mouse models were established by injecting D-galactose (Dgal). The estrous cycles were assessed through vaginal cytology, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), estradiol (E2), and progesterone (P) were measured by ELISA. The human ovarian granulosa cell line KGN was used for in vitro experiments. The uptake of hucMSC-EVs by KGN cells was detected. After D-gal treatment, cell proliferation and apoptosis were assessed via CCK-8 assay and flow cytometry. The PI3K/Akt pathway-related proteins were determined by Western blotting. Our results revealed that POF mice had prolonged estrous cycles, increased FSH and LH levels, and decreased AMH, E2, and P levels. Treatment with hucMSC-EVs partially counteracted the above changes. D-gal treatment reduced proliferation and raised apoptosis in KGN cells, while hucMSC-EV treatment annulled the changes. D-gal-treated cells exhibited downregulated p-PI3K/PI3K and p-Akt/Akt levels, while hucMSC-EVs activated the PI3K/Akt pathway. LY294002 suppressed the roles of hucMSC-EVs in promoting KGN cell proliferation and lowering apoptosis. Collectively, hucMSC-EVs facilitate proliferation and suppress apoptosis of ovarian granulosa cells by activating the PI3K/Akt pathway, thereby alleviating POF.
期刊介绍：
The Journal publishes original papers concerning investigations by histochemical and immunohistochemical methods, and performed with the aid of light, super-resolution and electron microscopy, cytometry and imaging techniques. Coverage extends to:
functional cell and tissue biology in animals and plants;
cell differentiation and death;
cell-cell interaction and molecular trafficking;
biology of cell development and senescence;
nerve and muscle cell biology;
cellular basis of diseases.
The histochemical approach is nowadays essentially aimed at locating molecules in the very place where they exert their biological roles, and at describing dynamically specific chemical activities in living cells. Basic research on cell functional organization is essential for understanding the mechanisms underlying major biological processes such as differentiation, the control of tissue homeostasis, and the regulation of normal and tumor cell growth. Even more than in the past, the European Journal of Histochemistry, as a journal of functional cytology, represents the venue where cell scientists may present and discuss their original results, technical improvements and theories.
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