Cheng Jing, Huang Jia, Yuan Suzhen, Zhou Su, Yan Wei, Shen Wei, Chen Yun, Xia Xi, Luo Aiyue, Zhu Da, Wang Shixuan
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R.China.
Ultrasonic Department, Peking University Shenzhen Hospital, Shenzhen, P.R.China.
PLoS One. 2017 Jun 23;12(6):e0177888. doi: 10.1371/journal.pone.0177888. eCollection 2017.
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.
环状RNA（circRNAs）是一类独特的内源性RNA，可作为多种疾病潜在的诊断和预后生物标志物。我们的研究旨在调查母体衰老过程中人类颗粒细胞（GCs）中的circRNA谱，并揭示与年龄相关的circRNA变化，这些变化可能反映卵母细胞能力下降。通过微阵列分析了年轻（YA，≤30岁）和高龄（AA，≥38岁）体外受精（IVF）患者GCs中的circRNAs，并在20对样本中进行了验证。在另外80个样本中分析了circRNAs表达与临床特征之间的相关性。基于芯片的分析显示，AA样本中有46个circRNAs上调，11个下调（倍数变化>2.0）。具体而言，circRNA_103829、circRNA_103827和circRNA_104816在AA样本中被验证为上调，而circRNA_101889下调。在调整促性腺激素治疗后，只有circRNA_103827和circRNA_104816的水平与产妇年龄呈正相关（偏相关系数r分别为0.332，P = 0.045；偏相关系数r为0.473，P = 0.003）。此外，GCs中circRNA_103827和circRNA_104816的表达与优质胚胎数量呈负相关（偏相关系数r分别为-0.235, P = 0.036；偏相关系数r为-0.221, P = 0.049）。受试者工作特征（ROC）曲线分析表明，circRNA_103827对活产预测的性能达到0.698 [0.570 - 0.825]，灵敏度为77.2%，特异性为60.9%（P = 0.006），circRNA_104816的性能为0.645 [0.507 - 0.783]（P = 0.043）。生物信息学分析表明，这两种circRNAs都可能参与葡萄糖代谢、有丝分裂细胞周期和卵巢类固醇生成。因此，circRNA_103827和circRNA_104816与年龄相关的上调可能是卵泡微环境受损的潜在指标，可以用来预测IVF预后，并改善女性不孕症的管理。
