Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications.
BACKGROUND
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.


METHODS
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.
Horcajadas
José A
JA
Fundación IVI-Instituto Universitario IVI-Universidad de Valencia, Valencia, Spain.
Mínguez
Pablo
P
Dopazo
Joaquín
J
Esteban
Francisco J
FJ
Domínguez
Francisco
F
Giudice
Linda C
LC
Pellicer
Antonio
A
Simón
Carlos
C
D000465:Algorithms; D006063:Chorionic Gonadotropin / Q000235:genetics; D004717:Endometrium / Q000166:cytology / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D008183:Luteal Phase / Q000502:physiology; D007986:Luteinizing Hormone / Q000235:genetics; D008597:Menstrual Cycle; D020411:Oligonucleotide Array Sequence Analysis; D010062:Ovulation Induction / Q000379:methods*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006063:Chorionic Gonadotropin; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D012313:RNA; D007986:Luteinizing Hormone; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase