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The aim of this study was to characterize the gene cooperation and regulation of menstrual cycle progression, 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.<\/jats:p>","DOI":"10.1093\/molehr\/gaab027","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T19:32:38Z","timestamp":1617823958000},"source":"Crossref","is-referenced-by-count":16,"title":["Transcriptional changes through menstrual cycle reveal a global transcriptional derepression underlying the molecular mechanism involved in the window of implantation"],"prefix":"10.1093","volume":"27","author":[{"given":"P","family":"Sebastian-Leon","sequence":"first","affiliation":[{"name":"Department of Genomic & Systems Reproductive Medicine, IVI-RMA IVI Foundation\u2014Instituto de Investigaci\u00f3n Sanitaria La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Devesa-Peiro","sequence":"additional","affiliation":[{"name":"Department of Genomic & Systems Reproductive Medicine, IVI-RMA IVI 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