Defects of microtubule cytoskeletal organization in NOA human testes.

Xiaolong Wu, Damin Yun, Mengmeng Sang, Jianpeng Liu, Liwei Zhou, Jie Shi, Lingling Wang, Tiao Bu, Linxi Li, YingYing Huang, Dengfeng Lin, Fei Sun, C Yan Cheng
{"title":"Defects of microtubule cytoskeletal organization in NOA human testes.","authors":"Xiaolong Wu,&nbsp;Damin Yun,&nbsp;Mengmeng Sang,&nbsp;Jianpeng Liu,&nbsp;Liwei Zhou,&nbsp;Jie Shi,&nbsp;Lingling Wang,&nbsp;Tiao Bu,&nbsp;Linxi Li,&nbsp;YingYing Huang,&nbsp;Dengfeng Lin,&nbsp;Fei Sun,&nbsp;C Yan Cheng","doi":"10.1186/s12958-022-01026-w","DOIUrl":null,"url":null,"abstract":"<p><p>The importance of actin and microtubule (MT) cytoskeletons in testis function in rodents is known to some extent, but its role in the etiology of azoospermia in humans remains unexplored. Here, we examined if MT cytoskeleton was defective in NOA (non-obstructive azoospermia) testes versus normal human testes based on histopathological, immunofluorescence (IF), and scRNA-Seq transcriptome profiling. Testis biopsy samples from n = 6 normal men versus n = 3 Sertoli cell only (SCO) and n = 3 MA (meiotic arrest) of NOA patients were used for histopathological analysis. IF analysis was also used to examine MT organization across the seminiferous epithelium, investigating the likely involvement of microtubule-associated proteins (MAPs). scRNA-Seq transcriptome profiling datasets from testes of 3 SCO patients versus 3 normal men in public domain in Gene Expression Omnibus (GEO) Sample (GSM) with identifiers were analyzed to examine relevant genes that regulate MT dynamics. NOA testes of MA and SCO patients displayed notable defects in MT organization across the epithelium with extensive truncation, mis-alignments and appeared as collapsed structures near the base of the tubules. These changes are in contrast to MTs in testes of normal men. scRNA-Seq analyses revealed considerable loss of spermatogenesis capacity in SCO testes of NOA patients versus normal men. An array of genes that support MT dynamics displayed considerable changes in expression and in spatial distribution. In summary, defects in MT cytoskeleton were noted in testes of NOA (SCO) patients, possibly mediated by defective spatial expression and/or distribution of MAPs. These changes, in turn, may impede spermatogenesis in SCO testes of NOA patients.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"154"},"PeriodicalIF":0.0000,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632130/pdf/","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive biology and endocrinology : RB&E","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12958-022-01026-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1

Abstract

The importance of actin and microtubule (MT) cytoskeletons in testis function in rodents is known to some extent, but its role in the etiology of azoospermia in humans remains unexplored. Here, we examined if MT cytoskeleton was defective in NOA (non-obstructive azoospermia) testes versus normal human testes based on histopathological, immunofluorescence (IF), and scRNA-Seq transcriptome profiling. Testis biopsy samples from n = 6 normal men versus n = 3 Sertoli cell only (SCO) and n = 3 MA (meiotic arrest) of NOA patients were used for histopathological analysis. IF analysis was also used to examine MT organization across the seminiferous epithelium, investigating the likely involvement of microtubule-associated proteins (MAPs). scRNA-Seq transcriptome profiling datasets from testes of 3 SCO patients versus 3 normal men in public domain in Gene Expression Omnibus (GEO) Sample (GSM) with identifiers were analyzed to examine relevant genes that regulate MT dynamics. NOA testes of MA and SCO patients displayed notable defects in MT organization across the epithelium with extensive truncation, mis-alignments and appeared as collapsed structures near the base of the tubules. These changes are in contrast to MTs in testes of normal men. scRNA-Seq analyses revealed considerable loss of spermatogenesis capacity in SCO testes of NOA patients versus normal men. An array of genes that support MT dynamics displayed considerable changes in expression and in spatial distribution. In summary, defects in MT cytoskeleton were noted in testes of NOA (SCO) patients, possibly mediated by defective spatial expression and/or distribution of MAPs. These changes, in turn, may impede spermatogenesis in SCO testes of NOA patients.

Abstract Image

Abstract Image

Abstract Image

NOA人类睾丸微管细胞骨架组织缺陷。
肌动蛋白和微管(MT)细胞骨架在啮齿类动物睾丸功能中的重要性在一定程度上是已知的,但其在人类无精子症病因学中的作用仍未被探索。在这里,我们基于组织病理学、免疫荧光(if)和scRNA-Seq转录组分析,检测了NOA(非阻塞性无精子症)睾丸中MT细胞骨架与正常人类睾丸相比是否存在缺陷。n = 6名正常男性的睾丸活检样本,n = 3名仅支持细胞(SCO)和n = 3名NOA患者的MA(减数分裂停止)样本用于组织病理学分析。IF分析也用于检查MT在精系上皮中的组织,研究微管相关蛋白(MAPs)的可能参与。我们分析了3名SCO患者和3名正常男性睾丸的scRNA-Seq转录组分析数据集,这些数据集来自基因表达综合样本(Gene Expression Omnibus Sample, GSM)中带有标识的公共领域,以检测调节MT动力学的相关基因。MA和SCO患者的NOA睾丸在上皮上表现出明显的MT组织缺陷,广泛截短,排列错位,在小管基部附近表现为塌陷结构。这些变化与正常男性睾丸中的MTs形成对比。scRNA-Seq分析显示,与正常男性相比,NOA患者SCO睾丸的精子发生能力明显下降。支持MT动态的一系列基因在表达和空间分布上显示出相当大的变化。总之,在NOA (SCO)患者的睾丸中发现了MT细胞骨架的缺陷,可能是由map的空间表达和/或分布缺陷介导的。这些变化反过来可能阻碍NOA患者SCO睾丸中的精子发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信