Transcriptional changes through menstrual cycle reveal a global transcriptional derepression underlying the molecular mechanism involved in the window of implantation

Fecha de publicación: 01/05/2021 Fecha Ahead of Print: 01/04/2021

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

Arnau V

Grupos

Biomarcadores, Medicina Genómica, Estadística y Análisis masivo de datos en Reproducción humana asistida

Investigador Principal

Marcos Meseguer Escrivá
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

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, 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.

Datos de la publicación

ISSN/ISSNe:: 1360-9947, 1460-2407
Tipo:: Article
Páginas:: -
DOI:: 10.1093/molehr/gaab027
Factor de Impacto:: 1,150 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Sebastian-Leon P:: Instituto de Investigación. IVI RMA IVI Fdn, Inst Invest Sanitaria La Fe, Dept Genom & Syst Reprod Med, Valencia, Spain
Devesa-Peiro A:: Instituto de Investigación. IVI RMA IVI Fdn, Inst Invest Sanitaria La Fe, Dept Genom & Syst Reprod Med, Valencia, Spain

Univ Valencia, Dept Pediat Obstet & Gynaecol, Valencia, Spain
Aleman A:: Instituto de Investigación. IVI RMA IVI Fdn, Inst Invest Sanitaria La Fe, Dept Genom & Syst Reprod Med, Valencia, Spain
Parraga-Leo A:: Instituto de Investigación. IVI RMA IVI Fdn, Inst Invest Sanitaria La Fe, Dept Genom & Syst Reprod Med, Valencia, Spain

Univ Valencia, Dept Pediat Obstet & Gynaecol, Valencia, Spain
Arnau V:: Univ Valencia, Escuela Tecn Super Ingn, Bioinformat, Burjassot, Spain

Univ Valencia, Consejo Super Invest Cient CSIC, Inst Integrat Syst Biol I2SysBio, Paterna, Spain
Pellicer A:: Instituto de Investigación. IVI RMA IVI Fdn, Inst Invest Sanitaria La Fe, Dept Genom & Syst Reprod Med, Valencia, Spain

Univ Valencia, Dept Pediat Obstet & Gynaecol, Valencia, Spain

IVI RMA IVI Rome, Reprod Med, Rome, Italy
Diaz-Gimeno P:: Instituto de Investigación. IVI RMA IVI Fdn, Inst Invest Sanitaria La Fe, Dept Genom & Syst Reprod Med, Valencia, Spain

Keywords

gene co-expression; weighted gene correlation network analysis (WGCNA); endometrial transcriptomics; endometrial receptivity; genetic regulation of menstrual cycle; nuclear hormone receptor; systems biology of the menstrual cycle; transcription factor; microRNA; recurrent implantation failure