Document Detail

Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis.
MedLine Citation:
PMID:  23284138     Owner:  NLM     Status:  MEDLINE    
Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons (n = 4) by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected during the midsecretory phase (Days 9-11 postovulation) at 1, 3, 6-7, 10-12, and 15-16 mo after disease induction and compared with tissue from disease-free baboons. RNA was hybridized to Human Genome U133 Plus 2.0 Arrays, and data were extracted using Gene-Chip Operating Software. Subsequently, both Gene Set Enrichment Analysis and Ingenuity Pathways Analysis were used to find biological states that have a statistically significant enrichment concomitant with pairwise comparison of human endometriosis arrays. Within 1 mo of induction of the disease, 4331 genes were differentially expressed (P < 0.05). Hierarchical clustering revealed self-segregation into two groups-a) 1, 3, and 10-12 mo and b) 6-7 and 15-16 mo-together with controls. Clustering analysis at each stage of disease validated dysregulation of several signaling pathways, including Nodal-like receptor, EGF, ERK/MAPK, and PI3/AKT. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype; however, as the disease progressed, a progesterone-resistant phenotype became evident. Furthermore, we demonstrate a 38.6% differential gene expression overlap with endometrial samples in the midsecretory phase from women with endometriosis, concomitant with similar dysregulation in human disease candidate genes Fos, Nodal, Suclg2, and Kras, among others. Molecular changes in the eutopic endometrium, associated with endometriosis, are directly impacted by endometriotic lesions, providing strong evidence that it is the disease rather than inherent defective endometrium that results in aberrant gene expression in the eutopic endometrium. Furthermore, this baboon model provides a powerful means whereby the early events associated with the pathology of disease and the resulting infertility may be elucidated.
Yalda Afshar; Julie Hastings; Damian Roqueiro; Jae-Wook Jeong; Linda C Giudice; Asgerally T Fazleabas
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-21
Journal Detail:
Title:  Biology of reproduction     Volume:  88     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-08-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44     Citation Subset:  IM    
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MeSH Terms
Disease Models, Animal
Disease Progression*
Endometriosis / genetics,  physiopathology*
Endometrium / physiopathology*
Epidermal Growth Factor / genetics,  physiology
Extracellular Signal-Regulated MAP Kinases / genetics,  physiology
Gene Expression Regulation / genetics,  physiology*
Mitogen-Activated Protein Kinase Kinases / genetics,  physiology
Oncogene Protein v-akt / genetics,  physiology
Papio anubis / genetics,  physiology*
Phosphatidylinositol 3-Kinases / genetics,  physiology
Signal Transduction / genetics,  physiology*
Time Factors
Grant Support
Reg. No./Substance:
62229-50-9/Epidermal Growth Factor; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Protein v-akt; EC Signal-Regulated MAP Kinases; EC Protein Kinase Kinases
Comment In:
Biol Reprod. 2013 Feb;88(2):43   [PMID:  23303683 ]

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