Almudena Devesa-Peiro1, Patricia Sebastian-Leon2, Francisco Garcia-Garcia3, Vicente Arnau4, Alejandro Aleman5, Antonio Pellicer6, Patricia Diaz-Gimeno7. 1. Department of Genomic and Systems Reproductive Medicine, IVI-RMA (Instituto Valenciano de Infertilidad, Reproductive Medicine Associates) IVI Foundation, Valencia, Spain; Department of Pediatrics, Obstetrics and Gynaecology, University of Valencia, Valencia, Spain. 2. Department of Genomic and Systems Reproductive Medicine, IVI-RMA (Instituto Valenciano de Infertilidad, Reproductive Medicine Associates) IVI Foundation, Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, University of Valencia, Valencia, Spain. 3. Unit of Bioinformatics and Biostatistics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. 4. Department of Computer Science, Escuela Técnica Superior de Ingenierías, University of Valencia, Burjassot, Spain, Institute for Integrative Systems Biology (I2SysBio), University of Valencia-CSIC, Paterna, Spain. 5. Department of Genomic and Systems Reproductive Medicine, IVI-RMA (Instituto Valenciano de Infertilidad, Reproductive Medicine Associates) IVI Foundation, Valencia, Spain. 6. Department of Pediatrics, Obstetrics and Gynaecology, University of Valencia, Valencia, Spain; IVI-RMA IVI Rome, Rome, Italy. 7. Department of Genomic and Systems Reproductive Medicine, IVI-RMA (Instituto Valenciano de Infertilidad, Reproductive Medicine Associates) IVI Foundation, Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, University of Valencia, Valencia, Spain. Electronic address: patricia.diaz@ivirma.com.
Abstract
OBJECTIVE: To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. DESIGN: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. SETTING: Infertility research department affiliated with a university hospital. PATIENT(S): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II-IV endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide gene expression and altered molecular functions in the endometrium of each uterine disorder. RESULT(S): Using robust analysis methods, we identified statistically significantly altered endometrial functions in all the uterine disorders. Cell cycle alterations were shared among all the pathologies investigated. Endometriosis was characterized by the down-regulation of ciliary processes. Among the endometriosis, ADC, and RIF samples, mitochondrial dysfunction and protein degradation were shared dysregulated processes. In addition, RPL had the most distinct functional profile, and 95% of affected functions were down-regulated. CONCLUSION(S): The most robust functions dysregulated in the endometrium of patients with uterine disorders across sample cohorts implicated an endometrial factor at the gene expression level. This shared endometrial factor affects endometrial receptivity processes.
OBJECTIVE: To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. DESIGN: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. SETTING:Infertility research department affiliated with a university hospital. PATIENT(S): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II-IV endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide gene expression and altered molecular functions in the endometrium of each uterine disorder. RESULT(S): Using robust analysis methods, we identified statistically significantly altered endometrial functions in all the uterine disorders. Cell cycle alterations were shared among all the pathologies investigated. Endometriosis was characterized by the down-regulation of ciliary processes. Among the endometriosis, ADC, and RIF samples, mitochondrial dysfunction and protein degradation were shared dysregulated processes. In addition, RPL had the most distinct functional profile, and 95% of affected functions were down-regulated. CONCLUSION(S): The most robust functions dysregulated in the endometrium of patients with uterine disorders across sample cohorts implicated an endometrial factor at the gene expression level. This shared endometrial factor affects endometrial receptivity processes.