Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor induced testicular function in dogs.
Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor induced testicular function in dogs.
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DOI：
10.1371/journal.pone.0099433
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dernell WS
中科院分区：
文献类型：
--
作者：
Kasimanickam VR;Kasimanickam RK;Dernell WS
精子发生是一个多步同步的过程。二倍体精原细胞经过有丝分裂、减数分裂和精子发生后，可分化为单倍体精子。雄性生殖细胞的分裂和分化是通过几个基因的顺序表达来实现的。在分化的生殖细胞中，许多mRNA经历转录后和翻译调节。MiRNA是mRNA转录、稳定性和翻译的强大负调控因子，并通过碱基配对识别其mRNA靶标。视黄酸（RA）信号传导对精子发生和睾丸功能至关重要。睾丸中RA的水平是RA信号转导的关键。本研究调查了与对照相比，给予全反式RA（2 µM）和CYP 26 B1抑制剂（1 µM）后RA诱导的睾丸环境中的miRNA调节。使用基于实时PCR的阵列技术分析了84种犬成熟miRNA，并区分了它们的表达特征。在分析的miRNA中，miRNA家族如miR-200（cfa-miR-200a、cfa-miR-200b和cfa-miR-200c），Mirlet-7（cfa-let-7a、cfa-let-7b、cfa-let-7c、cfa-let-7g和cfa-let-7f），miR-125（cfa-miR-125a和cfa-miR-125b）、miR-146（cfa-miR-146a和cfa-miR-146b）、miR-34（cfa-miR-34a、cfa-miR-34b和cfa-miR-34c）、miR-23（cfa-miR-23a和cfa-miR-23b），cfa-miR-184，cfa-miR-214和cfa-miR-141在通过给予CYP 26 B1抑制剂和全反式-RA的睾丸RA干预中显著上调，miR-19 a、cfa-miR-29 b、cfa-miR-29 c、cfa-miR-101和cfa-miR-137显著下调。本研究利用预测算法探索了有关染色体分布、人类正向序列和本研究中显著区分的miRNA家族靶基因相互作用的信息。这项研究重要地鉴定了RA诱导的精子发生引起的失调的miRNA种类。目前的贡献作为一个有用的资源，为进一步阐明单个miRNA在RA同步犬精子发生中的调节作用。
Spermatogenesis is a multistep synchronized process. Diploid spermatogonia differentiate into haploid spermatozoa following mitosis, meiosis and spermiogenesis. Division and differentiation of male germ cells is achieved through the sequential expression of several genes. Numerous mRNAs in the differentiating germ cells undergo post-transcriptional and translational regulation. MiRNAs are powerful negative regulators of mRNA transcription, stability, and translation and recognize their mRNA targets through base-pairing. Retinoic acid (RA) signaling is essential for spermatogenesis and testicular function. Testicular RA level is critical for RA signal transduction. This study investigated the miRNAs modulation in an RA- induced testicular environment following the administration of all-trans RA (2 µM) and CYP26B1- inhibitor (1 µM) compared to control. Eighty four canine mature miRNAs were analyzed and their expression signatures were distinguished using real-time PCR based array technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c), Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f), miR-125 (cfa-miR-125a and cfa-miR-125b), miR-146 (cfa-miR-146a and cfa-miR-146b), miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c), miR-23 (cfa-miR-23a and cfa-miR-23b), cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa-miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down-regulated. This study explored information regarding chromosome distribution, human orthologous sequences and the interaction of target genes of miRNA families significantly distinguished in this study using prediction algorithms. This study importantly identified dysregulated miRNA species resulting from RA-induced spermatogenesis. The present contribution serves as a useful resource for further elucidation of the regulatory role of individual miRNA in RA synchronized canine spermatogenesis.