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电纺垫构建的未成熟睾丸组织用于生物发光成像转基因小鼠模型的青春期前生育力保存。

Engineered Immature Testicular Tissue by Electrospun Mats for Prepubertal Fertility Preservation in a Bioluminescence Imaging Transgenic Mouse Model.

机构信息

Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei 110, Taiwan.

出版信息

Int J Mol Sci. 2022 Oct 12;23(20):12145. doi: 10.3390/ijms232012145.

DOI:10.3390/ijms232012145
PMID:36293000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9603635/
Abstract

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications.

摘要

青春期前患有癌症的男孩在接受性腺毒性化疗和放疗后可能会出现生育力和成熟度降低。因此,在这一人群中需要一种可行的未成熟睾丸组织 (ITT) 保存方法。在这项研究中,我们使用两种细度的聚 L-乳酸电纺支架来支持从转基因供体移植到野生型受体小鼠的 ITT 的发育。本研究的目的是评估使用这两种支架进行 ITT 移植和生精的潜力,采用生物发光成像进行评估。结果表明,来自 4 周龄小鼠的 ITT 在第 70 天具有最强的生精潜力,与精细电纺支架一起。此外,在受体小鼠中观察到生物发光成像强度长达 107 天,比粗电纺支架和对照组多约六倍。这是因为精细支架更类似于天然睾丸组织的微环境,因为它减少了由于微细化和体液渗透引起的刚性。热分析还显示在生物降解过程中发生再结晶,这可以导致更稳定的微环境。总的来说,这些发现为青春期前男性的生育力保存提供了前景,并可为未来的应用提供框架。

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