MicroRNA Expression is Altered in Granulosa Cells of Ovarian Hyperresponders
MicroRNA Expression is Altered in Granulosa Cells of Ovarian Hyperresponders
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DOI：
10.1177/1933719115625849
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发表时间：
2016-01
影响因子：
2.9
通讯作者：
Shi Xie;E. Batnasan;Qiong Zhang;Yanping Li
中科院分区：
文献类型：
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作者：
Shi Xie;E. Batnasan;Qiong Zhang;Yanping Li
控制性卵巢刺激在辅助生殖技术中起着不可或缺的作用，但个体患者对外源性促性腺激素的反应不同。为了确定microRNAs（miRNAs）是否在卵巢反应中具有调节作用，我们使用微阵列分析了从卵巢过度反应者和正常反应者中收集的分离的卵巢颗粒细胞中microRNAs的表达，并使用定量聚合酶链反应（PCR）验证了所选miRNAs的表达。两组之间有81个miRNAs差异表达，其中高反应组有45个增加，36个减少。对这些改变的miRNAs及其靶基因的生物信息学分析揭示了一些显著富集的通路，包括细胞周期、转录、细胞增殖和促性腺激素释放激素信号通路的调控。通过实时PCR验证hsa-miR-513 a-5 p、hsa-miR-27 b-3 p、hsa-miR-19 b-3 p、hsa-miR-3201、hsa-miR-423- 5 p、hsa-miR-193 b-5 p和hsa-miR-202- 3 p的表达。Hsa-miR-423- 5 p被预测为靶向抗苗勒管激素、细胞色素P450、家族19、亚家族A、多肽1、亚甲基四氢叶酸还原酶、孕酮受体和促卵泡激素β-多肽，发现其在高反应者中的表达显著降低（P = 0.023）。Hsa-miR-193 b-5 p在高反应者中也显示出显著降低的趋势（P = 0.093）。总之，我们的研究结果为卵巢高反应妇女颗粒细胞中miRNA表达的改变提供了证据，表明miRNA在调节卵巢对促性腺激素的反应中起作用。
Controlled ovarian stimulation plays an integral role in assisted reproduction technology, but individual patients have different responses to exogenous gonadotropins. In order to determine whether microRNAs (miRNAs) have a regulatory role in ovarian response, we profiled the expression of microRNAs in isolated ovarian granulosa cells collected from ovarian hyperresponders and normal responders using microarrays and validated the expression of selected miRNAs using quantitative polymerase chain reaction (PCR). There were 81 miRNAs differentially expressed between the 2 groups, with 45 increased and 36 decreased in the high response group. Bioinformatics analysis of these altered miRNAs and their target genes revealed some significantly enriched pathways, including regulation of the cell cycle, transcription, cell proliferation, and gonadotrophin releasing hormone signaling pathway. The expression of hsa-miR-513a-5p, hsa-miR-27b-3p, hsa-miR-19b-3p, hsa-miR-3201, hsa-miR-423-5p, hsa-miR-193b-5p, and hsa-miR-202-3p was validated by real-time PCR. Hsa-miR-423-5p, predicted to target anti-Mullerian hormone, cytochrome P450, family 19, subfamily A, polypeptide 1, methylenetetrahydrofolate reductase, progesterone receptor, and follicle stimulating hormone, β-polypeptide was found to have significantly decreased expression in the hyperresponders (P = .023). Hsa-miR-193b-5p also showed a tendency to be significantly decreased in the hyperresponders (P = .093). In conclusion, our findings provide evidence for altered miRNA expression in granulosa cells of women with ovarian hyperresponse, suggesting a role of miRNAs in regulating ovarian response to gonadotropins.