Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro

Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%− 50% of all infertility cases...

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Main Authors: Dezhi Yue, Fang Wang, Ying Han, Chengliang Xiong, Ruifeng Yang
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324001386
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author Dezhi Yue
Fang Wang
Ying Han
Chengliang Xiong
Ruifeng Yang
author_facet Dezhi Yue
Fang Wang
Ying Han
Chengliang Xiong
Ruifeng Yang
author_sort Dezhi Yue
collection DOAJ
description Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%− 50% of all infertility cases. Nonobstructive azoospermia (NOA) is the most severe type of male infertility. Human umbilical cord mesenchymal stem cell (hUCMSC) exosomes enhance proliferation and migration, playing crucial roles in tissue and organ injury repair. However, whether hUCMSC exosomes impacting on NOA caused by chemotherapeutic agents remains unknown. This study aimed to explore the functional restoration and mechanism of hUCMSC exosomes on busulfan-induced injury in GC-1 spg cells and ICR mouse testes. Our results revealed that hUCMSC exosomes effectively promoted the proliferation and migration of busulfan-treated GC-1 spg cells. Additionally, oxidative stress and apoptosis were significantly reduced when hUCMSC exosomes were treated. Furthermore, the injection of hUCMSC exosomes into the testes of ICR mice treated with busulfan upregulated the expression of mouse germ cell-specific genes, such as vasa, miwi, Stra8 and Dazl. Moreover, the expression of cellular junction- and cytoskeleton-related genes, including connexin 43, ICAM-1, β-catenin and androgen receptor (AR), was increased in the testicular tissues treated with exosomes. Western blot analysis demonstrated significant downregulation of apoptosis-associated proteins, such as bax and caspase-3, and upregulation of bcl-2 in the mouse testicular tissues injected with hUCMSC exosomes. Further, the spermatogenesis in the experimental group of mice injected with exosomes showed partial restoration of spermatogenesis compared to the busulfan-treated group. Collectively, these findings provide evidence for the potential clinical applications of hUCMSC exosomes in cell repair and open up new avenues for the clinical treatment of NOA.
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spelling doaj.art-e2333de5e824485084a022e912e694ba2024-02-22T04:51:32ZengElsevierEcotoxicology and Environmental Safety0147-65132024-03-01272116063Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitroDezhi Yue0Fang Wang1Ying Han2Chengliang Xiong3Ruifeng Yang4Reproductive Medicine Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, ChinaLaboratory Animal Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, ChinaLaboratory Animal Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaReproductive Medicine Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China; Correspondence to: Reproductive Medicine Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%− 50% of all infertility cases. Nonobstructive azoospermia (NOA) is the most severe type of male infertility. Human umbilical cord mesenchymal stem cell (hUCMSC) exosomes enhance proliferation and migration, playing crucial roles in tissue and organ injury repair. However, whether hUCMSC exosomes impacting on NOA caused by chemotherapeutic agents remains unknown. This study aimed to explore the functional restoration and mechanism of hUCMSC exosomes on busulfan-induced injury in GC-1 spg cells and ICR mouse testes. Our results revealed that hUCMSC exosomes effectively promoted the proliferation and migration of busulfan-treated GC-1 spg cells. Additionally, oxidative stress and apoptosis were significantly reduced when hUCMSC exosomes were treated. Furthermore, the injection of hUCMSC exosomes into the testes of ICR mice treated with busulfan upregulated the expression of mouse germ cell-specific genes, such as vasa, miwi, Stra8 and Dazl. Moreover, the expression of cellular junction- and cytoskeleton-related genes, including connexin 43, ICAM-1, β-catenin and androgen receptor (AR), was increased in the testicular tissues treated with exosomes. Western blot analysis demonstrated significant downregulation of apoptosis-associated proteins, such as bax and caspase-3, and upregulation of bcl-2 in the mouse testicular tissues injected with hUCMSC exosomes. Further, the spermatogenesis in the experimental group of mice injected with exosomes showed partial restoration of spermatogenesis compared to the busulfan-treated group. Collectively, these findings provide evidence for the potential clinical applications of hUCMSC exosomes in cell repair and open up new avenues for the clinical treatment of NOA.http://www.sciencedirect.com/science/article/pii/S0147651324001386Male infertilityUmbilical cord mesenchymal stem cellExosomeAzoospermia
spellingShingle Dezhi Yue
Fang Wang
Ying Han
Chengliang Xiong
Ruifeng Yang
Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
Ecotoxicology and Environmental Safety
Male infertility
Umbilical cord mesenchymal stem cell
Exosome
Azoospermia
title Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
title_full Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
title_fullStr Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
title_full_unstemmed Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
title_short Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
title_sort exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
topic Male infertility
Umbilical cord mesenchymal stem cell
Exosome
Azoospermia
url http://www.sciencedirect.com/science/article/pii/S0147651324001386
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AT yinghan exosomesderivedfromumbilicalcordmesenchymalstemcellsamelioratemaleinfertilitycausedbybusulfaninvivoandinvitro
AT chengliangxiong exosomesderivedfromumbilicalcordmesenchymalstemcellsamelioratemaleinfertilitycausedbybusulfaninvivoandinvitro
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