Establishment of a stem Leydig cell line capable of 11-ketotestosterone production.
Establishment of a stem Leydig cell line capable of 11-ketotestosterone production.
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DOI：
10.1071/rd20171
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Qin Huang;Zhuo Yang;Jie Wang;Yubing Luo;Changle Zhao;Minghui Li;Hesheng Xiao;W. Tao;
中科院分区：
文献类型：
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作者：
Qin Huang;Zhuo Yang;Jie Wang;Yubing Luo;Changle Zhao;Minghui Li;Hesheng Xiao;W. Tao;
雄激素缺乏或不足会引发一系列生殖疾病以及其他症状。在成年男性的一生中，干细胞对于形成和维持有功能的雄激素产生细胞(间质细胞，LC)群体至关重要。然而，到目前为止，我们对SLC的了解还很少。在这里，我们报告了一个能从3月龄尼罗罗非鱼(Oreochromis Niloticus)的睾丸中产生11-酮睾酮(11-KT)的克隆茎LC系(TSL)的来源和特征。传代77代后，细胞保持稳定增殖，核型正常，生长因子依赖。它们表达血小板衍生生长因子受体α(PDGFRα)、巢蛋白和鸡卵蛋白上游启动子转录因子II(COUP-TFIIA)，这是SLC的特征。在一定的诱导条件下，TSLs可以分化为具有类固醇激素活性的LCs，并产生11-KT。将PKH26标记的TSLs植入受体尼罗罗非鱼睾丸内，可以在间质中定植，随后表达类固醇合成基因，并恢复11-KT的产生。综上所述，我们的研究结果表明TSL具有持续增殖的能力，并有可能在体外和体内分化为功能性LCS。据我们所知，到目前为止，TSL可能是第一条能够生产11-KT的干式LC生产线。我们的研究可能为研究SLCs的自我更新和体外类固醇激素的生成提供新的机会，并为研究内分泌干扰物提供一个宝贵的体外模型。
The deficiency or insufficiency of androgen can trigger a range of reproductive diseases as well as other symptoms. Stem Leydig cells (SLCs) are critical for the formation and maintenance of a functional androgen-producing cell (Leydig cell, LC) population throughout adult male life. However, to date, our knowledge about SLCs is poor. Here we report the derivation and characterisation of a clonal stem LC line (designated as TSL) capable of 11- ketotestosterone (11-KT) production from a 3-month-old Nile tilapia (Oreochromis niloticus) testis. The cells retained stable proliferation after 77 generations with normal karyotype and growth factor dependency. They expressed platelet-derived growth factor receptor-α (pdgfrα), nestin and chicken ovalbumin upstream promoter transcription factor II (coup-tfIIa), which are characteristic of SLCs. Upon induction in defined medium, TSLs could undergo differentiation into steroidogenically active LCs and produce 11-KT. When implanted into recipient Nile tilapia testes from which endogenous LCs had been eliminated by ethane dimethanesulphonate (EDS) treatment, the PKH26-labelled TSLs could colonise the interstitium, subsequently express steroidogenic genes and restore 11-KT production. Taken together, our data suggest that TSLs possess the ability of continuous proliferation and potential of differentiation into functional LCs invitro and invivo. To the best of our knowledge TSL might represent the first stem LC line capable of 11-KT production to date. Our study may offer new opportunities for investigating the self-renewal of SLCs and steroidogenesis invitro, and provide an invaluable invitro model for investigating endocrine disruptors.