Insights into replicative senescence of human testicular peritubular cells
Insights into replicative senescence of human testicular peritubular cells
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深入了解人类睾丸管周细胞的复制衰老
DOI：
10.1038/s41598-019-51380-w
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发表时间：
2019
影响因子：
4.6
通讯作者：
Mayerhofer A.
中科院分区：
文献类型：
--
作者：
Schmid N;Flenkenthaler F;Stöckl JB;Dietrich KG;Köhn FM;Schwarzer JU;Kunz L;Luckner M;Wanner G;Arnold GJ;Fröhlich T;Mayerhofer A.
有证据表明男性生殖功能与年龄有关，但人类睾丸如何老化尚不清楚。人睾丸管周细胞（HTPCs）具有运输精子、维持精原干细胞（SSC）生态位和免疫监视等功能，可在体外进行分离和研究。HTPCs的复制性衰老的后果进行了评估，以获得人类睾丸老化的部分见解。为此，比较了早期和晚期HTPC传代，其中复制性衰老由细胞大小增加、核形态改变、β-半乳糖苷酶活性增强、端粒磨损和线粒体DNA（mtDNA）减少指示。这些变化通常是衰老细胞的典型特征。为了检查HTPC特异性变化，采用聚焦离子束扫描电子显微镜（FIB/SEM）断层扫描，其揭示了减少的线粒体网络和增加的溶酶体群体。结果与平行蛋白质组学分析的数据一致，并表明蛋白质稳态紊乱。典型的收缩性标志物和生长因子的mRNA水平，重要的SSC生态位，没有显着改变。然而，一项分泌组分析发现，巨噬细胞移动抑制因子（MIF）和二肽基肽酶4（DPP 4）的水平升高，这可能在精子发生中发挥作用。睾丸DPP 4可能进一步代表了一个可能的药物靶点。
There is evidence for an age-related decline in male reproductive functions, yet how the human testis may age is not understood. Human testicular peritubular cells (HTPCs) transport sperm, contribute to the spermatogonial stem cell (SSC) niche and immune surveillance, and can be isolated and studiedin vitro. Consequences of replicative senescence of HTPCs were evaluated to gain partial insights into human testicular aging. To this end, early and advanced HTPC passages, in which replicative senescence was indicated by increased cell size, altered nuclear morphology, enhanced β-galactosidase activity, telomere attrition and reduced mitochondrial DNA (mtDNA), were compared. These alterations are typical for senescent cells, in general. To examine HTPC-specific changes, focused ion beam scanning electron microscopy (FIB/SEM) tomography was employed, which revealed a reduced mitochondrial network and an increased lysosome population. The results coincide with the data of a parallel proteomic analysis and indicate deranged proteostasis. The mRNA levels of typical contractility markers and growth factors, important for the SSC niche, were not significantly altered. A secretome analysis identified, however, elevated levels of macrophage migration inhibitory factor (MIF) and dipeptidyl peptidase 4 (DPP4), which may play a role in spermatogenesis. Testicular DPP4 may further represent a possible drug target.
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影响因子：
9
作者：
Collin G;Huna A;Warnier M;Flaman JM;Bernard D
通讯作者：
Bernard D
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
深入了解雄激素受体在人睾丸管周细胞中的作用
影响因子：
4.5
作者：
C. Mayer;Marion Adam;Marion Adam;Lena Walenta;N. Schmid;Hanna Heikelä;K. Schubert;F. Flenkenthaler;K. Dietrich;S. Gruschka;G. Arnold;Thomas Fröhlich;J. Schwarzer;F. Köhn;L. Strauss;H. Welter;Matti Poutanen;Artur Mayerhofer
通讯作者：
Artur Mayerhofer
影响因子：
5.8
作者：
NIESCHLAG, E;LAMMERS, U;WICKINGS, EJ
通讯作者：
WICKINGS, EJ
影响因子：
5.5
作者：
M. Goto
通讯作者：
M. Goto