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哺乳动物Ste-20样激酶1/2(MST1/2)抑制剂XMU-MP-1:一种改善糖尿病小鼠模型精子发生的潜在化合物。

Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1: A Potential Compound to Improve Spermatogenesis in Mouse Model of Diabetes Mellitus.

作者信息

Amanda Bella, Faizah Zakiyatul, Pakpahan Cennikon, Aziz M Aminudin, Hamidah Berliana, Ashari Faisal Yusuf, Oceandy Delvac

机构信息

Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia.

Airlangga University Teaching Hospital, Universitas Airlangga, Surabaya 60115, Indonesia.

出版信息

Biomedicines. 2024 Nov 3;12(11):2513. doi: 10.3390/biomedicines12112513.

DOI:10.3390/biomedicines12112513
PMID:39595079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11591716/
Abstract

Spermatogenesis is a key process in male reproduction that, if it does not happen correctly, can lead to infertility, with diabetes being one of the most prevalent causes of spermatogenesis disruption. Currently, there is a lack of research examining the potential benefits of targeting cell proliferation to enhance spermatogenesis in this condition. XMU-MP1 has been identified as an inhibitor of MST1, a core component of the Hippo pathway, which is anticipated to promote proliferation and regeneration. This study aims to evaluate the effects of XMU-MP1 treatment on sperm and testicular characteristics in mice. We used the STZ-induced diabetic mouse model to investigate the impact of administering XMU-MP1 on testicular tissue and sperm parameters. This study compared the seminiferous tubules, specifically focusing on the diameter of the seminiferous tubule, the thickness of the seminiferous tubule epithelium, the ratio of the thickness of the seminiferous tubule epithelium to the diameter of the seminiferous tubules, and the lumen diameter of the seminiferous tubules. We also conducted a comparison of sperm parameters, including sperm concentration, progressive motility, total motility, total motility, and morphology. XMU-MP1-treated mice had a larger spermatogenesis area and better sperm motility than control mice. Diabetic mice treated with XMU-MP1 also showed a trend toward improvements in the spermatogenesis area, sperm concentration, sperm motility, and sperm morphology, although these improvements were not statistically significant. XMU-MP1 serves as a potential compound to improve spermatogenesis in mice.

摘要

精子发生是男性生殖中的关键过程,若该过程出现异常,可能导致不育,而糖尿病是精子发生紊乱的最常见原因之一。目前,针对在这种情况下通过靶向细胞增殖来增强精子发生的潜在益处的研究尚显不足。XMU-MP1已被确定为MST1(Hippo信号通路的核心组成部分)的抑制剂,预计其可促进细胞增殖和再生。本研究旨在评估XMU-MP1处理对小鼠精子及睾丸特征的影响。我们使用链脲佐菌素诱导的糖尿病小鼠模型来研究给予XMU-MP1对睾丸组织和精子参数的影响。本研究对生精小管进行了比较,特别关注生精小管的直径、生精小管上皮的厚度、生精小管上皮厚度与生精小管直径的比值以及生精小管的管腔直径。我们还对精子参数进行了比较,包括精子浓度、前向运动能力、总运动能力和形态。与对照小鼠相比,接受XMU-MP1处理的小鼠精子发生区域更大,精子运动能力更好。用XMU-MP1处理的糖尿病小鼠在精子发生区域、精子浓度、精子运动能力和精子形态方面也呈现出改善趋势,尽管这些改善在统计学上并不显著。XMU-MP1可作为一种潜在的化合物来改善小鼠的精子发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/e06e9747c0ae/biomedicines-12-02513-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/243895376a69/biomedicines-12-02513-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/98f56db93576/biomedicines-12-02513-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/bb9244e5bdb7/biomedicines-12-02513-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/6d681b7721f6/biomedicines-12-02513-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/a3db90d3bcf5/biomedicines-12-02513-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/2aec11d92c02/biomedicines-12-02513-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/bb3a6fb9dccb/biomedicines-12-02513-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/e06e9747c0ae/biomedicines-12-02513-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/243895376a69/biomedicines-12-02513-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/98f56db93576/biomedicines-12-02513-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/bb9244e5bdb7/biomedicines-12-02513-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/6d681b7721f6/biomedicines-12-02513-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/a3db90d3bcf5/biomedicines-12-02513-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/2aec11d92c02/biomedicines-12-02513-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/bb3a6fb9dccb/biomedicines-12-02513-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b98/11591716/e06e9747c0ae/biomedicines-12-02513-g008.jpg

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