Bisphenol A induced apoptosis and transcriptome differences of spermatogonial stem cells in vitro
Bisphenol A induced apoptosis and transcriptome differences of spermatogonial stem cells in vitro
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双酚A体外诱导精原干细胞凋亡及转录组差异
DOI：
10.1093/abbs/gmx075
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发表时间：
2017-09-01
影响因子：
3.7
通讯作者：
Lin, Yi
中科院分区：
文献类型：
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作者：
Gong, Xiaowen;Xie, Hui;Lin, Yi
双酚A(BPA)被广泛用作工业增塑剂，也是一种内分泌干扰物，被认为对生殖有不利影响。在雄性哺乳动物中，数十亿精子的长期生产依赖于精原干细胞(SSCs)的调控增殖和分化。然而，BPA对SSCs活性的影响知之甚少。为了探讨双酚A暴露对小鼠SSCs的影响，我们从小鼠体内分离SSCs，并成功地建立了SSCs的体外扩增模型。BPA处理后，我们发现BPA降低了SSC的存活率，并诱导了SSC的凋亡。为了揭示BPA处理的SSCs的转录组差异，我们进行了高通量RNA测序，发现在18,272个观察基因中有860个基因有差异表达。差异表达基因(Deg)丰富了调控细胞程序性死亡和细胞凋亡过程的基因本体论(GO)术语。在与京都基因和基因组百科全书(KEGG)的凋亡途径相关的一组DEG中，激活转录因子4(ATF4)和DNA损伤诱导转录因子3(DDIT3)基因在BPA处理的SSCs中显著上调，qPCR证实。综上所述，这些发现提示BPA可通过诱导SSCs的凋亡而增加促凋亡基因的mRNA表达，降低SSCs的存活率。
Bisphenol A (BPA) is widely used as an industrial plasticizer, which is also an endocrine disruptor and considered to have adverse effects on reproduction. In male mammals, the long-term production of billions of spermatozoa relies on the regulated proliferation and differentiation of spermatogonial stem cells (SSCs). However, little is known about the effects of BPA on the viability of SSCs. To investigate the influence of BPA exposure on SSCs in vitro, we isolated SSCs from mouse and successfully established in vitro propagation of SSCs. After BPA treatment, we found that BPA reduced the viability of SSCs and induced SSC apoptosis. For revealing the transcriptome differences of the BPA-treated SSCs, we performed high-throughput RNA sequencing and found that 860 genes were differentially expressed among 18,272 observed genes. The gene ontology (GO) terms, regulation of programmed cell death and apoptotic process, were enriched in the differentially expressed genes (DEGs). Among the cluster of DEGs associated with the kyoto encyclopedia of genes and genomes (KEGG) apoptosis pathway, activating transcription factor 4 (Atf4) and DNA damage inducible transcript 3 (Ddit3) genes were significantly up-regulated in BPA-treated SSCs, which were proved by qPCR. Taken together, these findings suggest that BPA can increase the mRNA expression of pro-apoptosis genes and reduce the viability of SSCs by inducing apoptosis.