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RESEARCH PRODUCT

Controlled Ovarian Stimulation Induces a Functional Genomic Delay of the Endometrium with Potential Clinical Implications

Linda C. GiudiceJosé A. HorcajadasAntonio PellicerPablo MinguezCarlos SimónJoaquín DopazoFrancisco DomínguezFrancisco J. Esteban

subject

medicine.medical_specialtyendocrine systemEndocrinology Diabetes and Metabolismmedia_common.quotation_subjectClinical BiochemistryStimulationLuteal PhaseBiologyEndometriumChorionic GonadotropinBiochemistryHuman chorionic gonadotropinEndometriumEndocrinologyOvulation InductionReference ValuesInternal medicinemedicineHumansMenstrual CycleMenstrual cycleOligonucleotide Array Sequence Analysismedia_commonRegulation of gene expressionGlutathione PeroxidaseGenome HumanReverse Transcriptase Polymerase Chain ReactionMicroarray analysis techniquesurogenital systemBiochemistry (medical)Luteinizing HormoneInsulin-Like Growth Factor Binding ProteinsGene expression profilingInsulin-Like Growth Factor Binding Protein 3Endocrinologymedicine.anatomical_structureGene Expression RegulationGene chip analysisRNAFemaleAlgorithms

description

Context: Controlled ovarian stimulation induces morphological, biochemical, and functional genomic modifications of the human endometrium during the window of implantation. Objective: Our objective was to compare the gene expression profile of the human endometrium in natural vs. controlled ovarian stimulation cycles throughout the early-mid secretory transition using microarray technology. Method: Microarray data from 49 endometrial biopsies obtained from LH+1 to LH+9 (n = 25) in natural cycles and from human chorionic gonadotropin (hCG) +1 to hCG+9 in controlled ovarian stimulation cycles (n = 24) were analyzed using different methods, such as clustering, profiling of biological processes, and selection of differentially expressed genes, as implemented in Gene Expression Pattern Analysis Suite and Babelomics programs. Results: Endometria from natural cycles followed different genomic patterns compared with controlled ovarian stimulation cycles in the transition from the pre-receptive (days LH/hCG+1 until LH/hCG+5) to the receptive phase (day LH+7/hCG+7). Specifically, we have demonstrated the existence of a 2-d delay in the activation/repression of two clusters composed by 218 and 133 genes, respectively, on day hCG+7 vs. LH+7. Many of these delayed genes belong to the class window of implantation genes affecting basic biological processes in the receptive endometrium. Conclusions: These results demonstrate that gene expression profiling of the endometrium is different between natural and controlled ovarian stimulation cycles in the receptive phase. Identification of these differentially regulated genes can be used to understand the different developmental profiles of receptive endometrium during controlled ovarian stimulation and to search for the best controlled ovarian stimulation treatment in terms of minimal endometrial impact.

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