Fundación IVIInstituto Universitario IVI, Universidad de Valencia, Valencia, Spain.
Instituto de Investigación Sanitaria INCLIVAValencia, Spain.
Reproduction. 2018 Apr;155(4):373-381. doi: 10.1530/REP-18-0027. Epub 2018 Feb 9.
Polycystic ovarian syndrome (PCOS) is a common reproductive disorder frequently associated with a substantial risk factor for ovarian hyperstimulation syndrome (OHSS). Dopamine receptor 2 (D2) agonists, like cabergoline (Cb2), have been used to reduce the OHSS risk. However, lutein granulosa cells (LGCs) from PCOS patients treated with Cb2 still show a deregulated dopaminergic tone (decreased D2 expression and low dopamine production) and increased vascularization compared to non-PCOS LGCs. Therefore, to understand the PCOS ovarian physiology, it is important to explore the mechanisms that underlie syndrome based on the therapeutic effects of Cb2. Here, LGCs from non-PCOS and PCOS patients were cultured with hCG in the absence/presence of Cb2 ( = 12). Subsequently, a transcriptomic-paired design that compared untreated vs treated LGCs within each patient was performed. After transcriptomic analysis, functions and genes were prioritized by systems biology approaches and validated by RT-qPCR. We identified that similar functions were altered in both PCOS and non-PCOS LGCs treated with Cb2; however, PCOS-treated LGCs exhibited more significant changes than non-PCOS. Among the prioritized functions, dopaminergic synapse, vascular endothelial growth factor (VEGF) signaling, apoptosis and ovarian steroidogenesis were highlighted. Finally, network modeling showed , , , , , , and as key genes implicated in these pathways in Cb2 response, which might be potential biomarkers for further studies in PCOS.
多囊卵巢综合征（PCOS）是一种常见的生殖系统疾病，常伴有卵巢过度刺激综合征（OHSS）的高风险因素。多巴胺受体 2（D2）激动剂，如卡麦角林（Cb2），已被用于降低 OHSS 的风险。然而，与非 PCOS 患者的颗粒黄体细胞（LGC）相比，接受 Cb2 治疗的 PCOS 患者的 LGC 仍然表现出多巴胺能张力失调（D2 表达降低和多巴胺产生减少）和血管生成增加。因此，为了了解 PCOS 的卵巢生理学，探索基于 Cb2 治疗效果的综合征的机制非常重要。在这里，用 hCG 培养非 PCOS 和 PCOS 患者的 LGC，有无 Cb2（ = 12）。随后，对每个患者未经处理的 vs 处理的 LGC 进行了转录组配对设计。转录组分析后，通过系统生物学方法对功能和基因进行了优先级排序，并通过 RT-qPCR 进行了验证。我们发现，用 Cb2 处理的 PCOS 和非 PCOS 的 LGC 都改变了相似的功能；然而，PCOS 治疗的 LGC 比非 PCOS 的 LGC 表现出更显著的变化。在优先考虑的功能中，多巴胺能突触、血管内皮生长因子（VEGF）信号转导、细胞凋亡和卵巢甾体生成作用突出。最后，网络建模显示 、 、 、 、 、 、 和 是 Cb2 反应中这些途径的关键基因，它们可能是 PCOS 进一步研究的潜在生物标志物。
