Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel.
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland.
Int J Mol Sci. 2021 Jul 30;22(15):8216. doi: 10.3390/ijms22158216.
Granulosa-lutein cells (GLCs) from PCOS women display reduced and levels, suggesting their role in PCOS etiology. Here, we investigated the mechanisms involved in aberrant expression in PCOS, and its association with . Various -dependent factors were studied in GLCs from PCOS and compared to normally ovulating women. MicroRNA-210 (miR-210), its target genes ( and ), and -responsive genes ( and ) differed in GLCs from PCOS, compared with those of healthy women. Levels of miR-210-designated hypoxiamiR-and were reduced in the PCOS GLCs; concomitantly, and levels were elevated. Cultured GLCs retained low expression and had low levels, providing evidence for a disrupted hypoxic response in the PCOS GLCs. However, expression was elevated in these cells. Next, miR-210 levels were manipulated. miR-210-mimic stimulated twice as much as the miR-NC-transfected cells, whereas miR-210-inhibitor diminished emphasizing the importance of hypoxiamiR for induction. Intriguingly, transcripts were reduced by both miR-210-mimic and -inhibitor, demonstrating that and are distinctly regulated. Disrupted hypoxic response in the GLCs of periovulatory follicles in PCOS women may play a role in ovulation failure, and in the reduced fertility prevalent in this syndrome.
多囊卵巢综合征（PCOS）患者的颗粒细胞黄体细胞（GLCs）显示出 和 水平降低，表明它们在 PCOS 发病机制中的作用。在这里，我们研究了 PCOS 中异常 表达的相关机制及其与 的关系。在 PCOS 和正常排卵女性的 GLCs 中研究了各种 依赖性因素。与健康女性相比，PCOS GLCs 中的 microRNA-210（miR-210）、其靶基因（ 和 ）和 反应基因（ 和 ）存在差异。PCOS GLCs 中 miR-210 标记的低氧 miRNA 和 的水平降低，而 和 的水平升高。培养的 GLCs 保持低 表达，并且 水平较低，这为 PCOS GLCs 中缺氧反应受损提供了证据。然而，这些细胞中的 表达升高。接下来，操纵了 miR-210 的水平。miR-210 模拟物刺激 的表达是 miR-NC 转染细胞的两倍，而 miR-210 抑制剂则减少了 ，这强调了低氧 miRNA 对 诱导的重要性。有趣的是，miR-210 模拟物和抑制剂都减少了 转录本，表明 和 受到明显的调节。PCOS 女性排卵前卵泡 GLCs 中缺氧反应受损可能在排卵失败和该综合征中普遍存在的生育力降低中发挥作用。
