Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria.
The expression of human CYR61 (cysteine-rich, angiogenic inducer, 61; CCN1) mRNA has been previously shown to be deregulated in the endometrium of women with endometriosis. We have chosen the baboon model (Papio anubis) of induced endometriosis to clarify whether CYR61 mRNA upregulation is predisposed to an inappropriately differentiated endometrium or is deregulated as a response to the presence of ectopic lesions. In the baboon, endometrial CYR61 mRNA expression underwent moderate cyclical variation, with a significant 7.3-fold increase detected at Day 2 postmenses when compared to endometrium from the proliferative and secretory phases. The CYR61 transcript was extensively upregulated in the eutopic endometrium from all baboons with induced endometriosis, as early as 1 mo postinoculation of menstrual tissue into the peritoneal cavity. CYR61 mRNA expression then decreased throughout progression of the disease, but remained higher compared to control tissues. Ectopic endometriotic lesions showed a further increase in CYR61 mRNA, with highest expression found in red lesions. Moreover, the expression levels of CYR61 transcripts correlated significantly with those of VEGF. Immunohistochemistry revealed the presence of CYR61 protein in glandular and luminal epithelial cells as well as in blood vessels of eutopic and ectopic endometrium. As in humans, increased levels of CYR61 mRNA correlated with the development of endometriosis in baboons. The increase of CYR61 mRNA in eutopic endometrium of baboons following peritoneal inoculation with menstrual endometrium provides evidence for a feedback mechanism from resulting lesions to induce a shift in gene expression patterns in the eutopic endometrium.
University of Duisburg-Essen, Institute of Anatomy, 45122 Essen, Germany. isabella.gashaw@uni-essen.de
Isabella
I
Gashaw
Julie M
JM
Hastings
Kevin S
KS
Jackson
Elke
E
Winterhager
Asgerally T
AT
Fazleabas
D000818:Animals; D002828:Choristoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004715:Endometriosis / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004717:Endometrium / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics* / Q000502:physiology; D048530:Papio anubis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000502:physiology
D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A