The human endometrium is a dynamic tissue that only is receptive to host the embryo during a brief time in the middle secretory phase, called the window of implantation (WOI). Despite its importance, regulation of the menstrual cycle remains incompletely understood. The aim of this study was to characterize the gene cooperation and regulation of menstrual cycle progression, in order to dissect the molecular complexity underlying acquisition of endometrial receptivity for a successful pregnancy; and to provide the scientific community with detailed gene co-expression information throughout the menstrual cycle on a user-friendly web-tool database. A retrospective gene co-expression analysis was performed based on the endometrial receptivity array (ERarray) gene signature from 523 human endometrial samples collected across the menstrual cycle, including during the WOI. Gene co-expression analysis revealed the WOI as having the significantly smallest proportion of negative correlations for transcriptional profiles associated with successful pregnancies compared to other cycle stages, pointing to a global transcriptional derepression being involved in acquisition of endometrial receptivity. Regulation was greatest during the transition between proliferative and secretory endometrial phases. Further, we prioritized nuclear hormone receptors as major regulators of this derepression and proved that some genes and transcription factors involved in this process were dysregulated in patients with recurrent implantation failure. We also compiled the wealth of gene co-expression data to stimulate hypothesis-driven single-molecule endometrial studies in a user-friendly database: Menstrual Cycle Gene Co-expression Network (www.menstrualcyclegcn.com). This study revealed a global transcriptional repression across the menstrual cycle, which relaxes when the WOI opens for transcriptional profiles associated with successful pregnancies. These findings suggest that a global transcriptional derepression is needed for embryo implantation and early development.

中文翻译：

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通过月经周期的转录变化揭示了植入转录窗口中涉及的分子机制的整体转录抑制。

人子宫内膜是一种动态组织，仅在中间分泌阶段的短暂时间内接受宿主胚胎，称为植入窗口（WOI）。尽管很重要，但对月经周期的调节仍未完全了解。这项研究的目的是表征基因合作和月经周期进展的调节，以剖析成功获得妊娠子宫内膜接受性的分子复杂性。并在用户友好的网络工具数据库上为科学界提供整个月经周期中详细的基因共表达信息。根据从整个月经周期收集的523份人类子宫内膜样品中的子宫内膜接受性阵列（ERarray）基因签名进行了回顾性基因共表达分析，包括在WOI期间。基因共表达分析显示，与其他周期阶段相比，WOI与成功妊娠相关的转录谱具有显着最小的负相关比例，这表明子宫内膜接受性的获得涉及整体转录抑制。在增生期和分泌性子宫内膜期之间的过渡过程中，调节作用最大。此外，我们将核激素受体优先作为该抑制的主要调节剂，并证明在反复植入失败的患者中，参与该过程的某些基因和转录因子失调。我们还在用户友好的数据库中收集了大量基因共表达数据，以刺激假设驱动的单分子子宫内膜研究：月经周期基因共表达网络（www.menstrualcyclegcn.com）。这项研究揭示了整个月经周期的整体转录抑制，当WOI打开与成功妊娠相关的转录特征时，这种抑制会放松。这些发现表明胚胎植入和早期发育需要全局转录抑制。