Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes.
Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes.
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母亲衰老过程中人类颗粒细胞的环状 RNA 表达谱揭示了与辅助生殖技术结果相关的新转录本
DOI：
10.1371/journal.pone.0177888
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Cheng J;Huang J;Yuan S;Zhou S;Yan W;Shen W;Chen Y;Xia X;Luo A;Zhu D;Wang S
环状RNA（CircRNA）是一类独特的内源性RNA，可作为多种疾病的潜在诊断和预后生物标志物。我们的研究旨在调查人类颗粒细胞（GC）在母体衰老过程中的circRNA谱，并揭示年龄相关的circRNA变异，这些变异可能反映了卵母细胞能力的下降。采用微阵列技术检测年轻（YA，≤ 30岁）和高龄（AA，≥ 38岁）体外受精（IVF）患者GCs中的CircRNA，并在20个配对样本中进行验证。在另外80个样本中分析circRNA表达与临床特征之间的相关性。基于芯片的分析揭示了AA样品中46个上调和11个下调的circRNA（倍数变化> 2.0）。具体而言，在AA样品中，circRNA_103829、circRNA_103827和circRNA_104816被验证为上调，而circRNA_101889被下调。调整促性腺激素治疗后，仅circRNA_103827和circRNA_104816水平与母亲年龄正相关（部分r = 0.332，P = 0.045;部分r = 0.473，P = 0.003;分别）。此外，GC中circRNA_103827和circRNA_104816的表达与优质胚胎数呈负相关（分别为r =-0.235，P = 0.036; r =-0.221，P = 0.049）。受试者工作特征（ROC）曲线分析显示，circRNA_103827预测活产的性能为0.698 [0.570-0.825]，敏感性为77.2%，特异性为60.9%（P = 0.006），circRNA_104816为0.645 [0.507-0.783]（P = 0.043）。生物信息学分析表明，这两个circRNA可能参与葡萄糖代谢，有丝分裂细胞周期，和卵巢类固醇激素的生成。因此，circRNA_103827和circRNA_104816的年龄相关性上调可能是卵泡微环境受损的潜在指标，可用于预测IVF预后，并改善女性不孕症的管理。
Circular RNAs (circRNAs) are a unique class of endogenous RNAs which could be used as potential diagnostic and prognostic biomarkers of many diseases. Our study aimed to investigate circRNA profiles in human granulosa cells (GCs) during maternal aging and to uncover age-related circRNA variations that potentially reflect decreased oocyte competence. CircRNAs in GCs from in vitro fertilization (IVF) patients with young age (YA, ≤ 30 years) and advanced age (AA, ≥ 38 years) were profiled by microarray, and validated in 20 paired samples. The correlation between circRNAs expression and clinical characteristics was analyzed in additional 80 samples. Chip-based analysis revealed 46 up-regulated and 11 down-regulated circRNAs in AA samples (fold change > 2.0). Specifically, circRNA_103829, circRNA_103827 and circRNA_104816 were validated to be up-regulated, while circRNA_101889 was down-regulated in AA samples. After adjustment for gonadotropin treatment, only circRNA_103827 and circRNA_104816 levels were positively associated with maternal age (partial r = 0.332, P = 0.045; partial r = 0.473, P = 0.003; respectively). Moreover, circRNA_103827 and circRNA_104816 expressions in GCs were negatively correlated with the number of top quality embryos (r = -0.235, P = 0.036; r = -0.221, P = 0.049; respectively). Receiver operating characteristic (ROC) curve analysis indicated that the performance of circRNA_103827 for live birth prediction reached 0.698 [0.570–0.825], with 77.2% sensitivity and 60.9% specificity (P = 0.006), and that of circRNA_104816 was 0.645 [0.507–0.783] (P = 0.043). Bioinformatics analysis revealed that both circRNAs were potentially involved in glucose metabolism, mitotic cell cycle, and ovarian steroidogenesis. Therefore, age-related up-regulation of circRNA_103827 and circRNA_104816 might be potential indicators of compromised follicular micro-environment which could be used to predict IVF prognosis, and improve female infertility management.