Exosomes of mesenchymal stem cells and PRP restore spermatogenesis in the rat model of non-obstructive azoospermia.

IF 3.7 3区生物学 Q1 DEVELOPMENTAL BIOLOGY

Reproduction Pub Date : 2024-08-12 Print Date: 2024-09-01 DOI:10.1530/REP-23-0474

Azar Sheikholeslami, Faezeh Davoodi Asl, Hoda Fazaeli, Mohsen Sheykhhasan, Naser Kalhor, Leila Naserpour

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引用次数: 0

Abstract

In brief: Since available therapeutic approaches for chemotherapy-induced non-obstructive azoospermia (NOA) patients are not enough efficient, an urgent need for treatment alternatives is felt. This study shows that adipose tissue-derived mesenchymal stem cells-derived exosome (AD-Exo) treatment is more effective in ameliorating busulfan-induced NOA rat models compared to platelet-rich plasma (PRP).

Abstract: Patients with non-obstructive azoospermia (NOA) are unable to have their children. Therefore, there is an urgent need for additional treatment alternatives for these patients. Recently, novel treatments based on the exosomes derived from mesenchymal stem cells (MSCs) as the agents responsible for exerting the paracrine effects and consequently biological functions of MSCs are proposed. Besides, platelet-rich plasma (PRP) as a significant blood byproduct has been therapeutically applied in several male infertility studies. In this study, we compared the effects of PRP and exosome treatment on spermatogenesis restoration in NOA rat models. Exosomes and PRP were isolated from the adipose tissue-derived MSCs (AD-MSCs) collected from conditioned medium and peripheral blood of human volunteers, respectively. Non-obstructive azoospermia (NOA) induction was done through two doses of busulfan at a 21-day interval. Thirty-five days after NOA induction, intratesticular injection of AD-MSCs-derived exosome (AD-Exo), PRP, and PBS was performed. The control group did not receive any treatment. Two months later, the rats were euthanized for further analysis. Our results revealed that both AD-Exo and PRP treatments improved the size and weight of testis, modulated the expression level of Dazl, Ddx4, Stra8, Pwil1, and Ccna1, and ameliorated the serum level of LDH, SOD, and GR enzymes in NOA rats. Moreover, the AD-Exo group showed improved testosterone, GPx, MAD, and CAT serum levels, sperm motility, and protein levels of DAZL and DDX4. This investigation verified the more efficient effects of AD-Exo treatment in comparison to PRP in ameliorating busulfan-induced NOA rat models.

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间充质干细胞外泌体和PRP可恢复大鼠非梗阻性无精子症模型的精子发生。

非梗阻性无精子症（NOA）患者无法生育。因此，这些患者迫切需要更多的替代治疗方法。最近，有人提出了基于间充质干细胞（MSCs）外泌体的新型疗法，这种外泌体可发挥间充质干细胞的旁分泌效应，从而发挥间充质干细胞的生物功能。此外，富血小板血浆（PRP）作为一种重要的血液副产品，已在多项男性不育症研究中得到应用。在本研究中，我们比较了 PRP 和外泌体治疗对 NOA 大鼠精子发生恢复的影响。外泌体和PRP分别从条件培养基和人类志愿者外周血中收集的脂肪组织间充质干细胞（AD-MSCs）中分离出来。NOA诱导是通过两次剂量的硫胺素（间隔 21 天）完成的。在NOA诱导35天后，进行睾丸内注射AD-间充质干细胞衍生的外泌体（AD-Exo）、PRP和PBS。对照组不接受任何治疗。两个月后，大鼠被安乐死，以便进行进一步分析。结果显示，AD-Exo 和 PRP 治疗均改善了 NOA 大鼠睾丸的大小和重量，调节了 Dazl、Ddx4、Stra8、Pwil1 和 CyclinA1 的表达水平，并改善了血清中 LDH、SOD 和 GR 酶的水平。此外，AD-Exo 组的睾酮、GPx、MAD 和 CAT 血清水平、精子活力以及 Dazl 和 Ddx4 蛋白水平均有所提高。这项研究证实，与 PRP 相比，AD-Exo 治疗对改善硫丹诱导的 NOA 大鼠模型具有更有效的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproduction 生物-发育生物学

CiteScore

7.40

自引率

2.60%

发文量

199

审稿时长

4-8 weeks

期刊介绍： Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction. Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease. Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.