[Study of tissue morphology and vascular endothelial growth factor and matrix metalloproteinase-9 gene expressions in nude mouse endometriosis model].
OBJECTIVE
To establish an experimental endometriosis model using nude mouse as a xenographic host for relative biological behavior study of endometriosis.


METHODS
Nude mice of experimental group were implanted with the late secretory endometrium of patients with endometriosis (n = 24) or without endometriosis (n = 24) into pelvic and abdominal cavities. Nude mice of control group (n = 3) were implanted with the greater omentum. Nude mice were killed at 5, 15 and 30 d randomly to observe the growth of endometriotic lesions. The morphological changes of endometriotic lesions from different sources and at different time points of growth were examined by light microscopy and electron microscopy; the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) of eutopic endometrium and endometriotic lesions were detected by RT-PCR method, and the expressions of steroid hormone receptors by immunohistochemistry method.


RESULTS
Endometriotic lesions were found from 5 d with rich blood supply, endometrial glands and stroma under light microscope. And the adhesion to mouse tissues became more severe with time. Under electron microscope, proliferation and infiltration of inflammatory cells were most striking at 15 d. At 30 d the organellae of gland cells were disappeared and there was nuclear chromatin aggregation with apoptosis tendency, but secretory granules still could be seen. The expressions of VEGF and MMP-9 mRNA were increased in endometriotic lesions compared with eutopic endometrium (P < 0.05), and were strongest at 15 d (EM group: 1.11 +/- 0.13/1.00 +/- 0.11; NEM group: 1.10 +/- 0.11/0.99 +/- 0.08) and decreased at 30 d (EM group: 0.85 +/- 0.11/0.77 +/- 0.13; NEM group: 0.86 +/- 0.14/0.76 +/- 0.11). Immunochemistry revealed the positive rate of estrogen and progestogen receptors at 30 d (EM group: 4/8 and 4/8; NEM group: 5/8 and 4/8) was lower than that at 5 d (EM group: 7/8 and 7/8; NEM group: 8/8 and 7/8) and 15 d (EM group: 7/8 and 7/8; NEM group: 7/8 and 8/8), and the expressions of steroid hormone receptors were mostly weak. There was no differences in expression of VEGF and MMP-9 mRNA, estrogen and progestogen between endometriotic lesions implanted with normal endometrium and endometrium from patients with endometriosis.


CONCLUSIONS
The nude mouse is an appropriate model for the study of the early phase of endometriosis, and the genesis and development of endometriotic lesions are similar to that of human endometriosis. Endometriosis is associated with multiple factors.
Wang
Dan-Bo
DB
Department of Obstetrics and Gynecology, Second Affiliated Hospital of China Medical University, Shenyang 110004, China.
Zhang
Shu-Lan
SL
Niu
Hui-Yan
HY
Lu
Jing-Ming
JM
D000818:Animals; D004195:Disease Models, Animal; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9