Role of immunoreactions and mast cells in pathogenesis of human endometriosis--morphologic study and gene expression analysis.
OBJECTIVE
To investigate the pathophysiology of human endometriosis, we examined by morphological and molecular biological methods.


METHODS
Samples of ovarian endometriosis and normal ovarian tissues were obtained laparoscopically after informed consent. A morphological study by toluidine blue staining, immunohistochemistry of c-kit and electron microscopy demonstrated the localization of mast cells in the stromal lesions of endometriosis. Oligonucleotide microarrays were used for gene expression analysis.


RESULTS
Infiltration of numerous mast cells and development of fibrosis was observed throughout the stromal lesions. Gene expression analysis by oligonucleotide microarrays indicated inflammatory immunoreactions in the lesions. Expressions of the FCER1G and PGDS, which are considered to be mast cell-specific genes, were upregulated in the ovarian endometriotic lesions as compared to the normal ovarian tissues. Furthermore, expressions of genes associated with immunological inflammation, such as IL-8, GRO1, GRO2, CXCR4, MCP1, and those related to tissue remodeling (MMP, COL4A2, and COL5A2) were also higher in endometriotic lesions than in the normal ovarian tissue.


CONCLUSIONS
Thus it is likely that mast cells and their related inflammatory immunoreactions via chemokines play important roles in producing fibrosis and adhesions in endometriotic lesions.
Department of Gynecology, Omiya Medical Center, Jichi Medical School, Amanuma-cho, Omiya, Saitama, Japan. kryo77@excite.co.jp
Ryo
R
Konno
Hisafumi
H
Yamada-Okabe
Hiroyuki
H
Fujiwara
Ichiro
I
Uchiide
Hiroaki
H
Shibahara
Michitaka
M
Ohwada
Tomomi
T
Ihara
Masao
M
Sugamata
Mitsuaki
M
Suzuki
D018925:Chemokines / Q000378:metabolism*; D004715:Endometriosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000276:immunology / Q000473:pathology*; D008854:Microscopy, Electron; D020411:Oligonucleotide Array Sequence Analysis; D010049:Ovarian Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015854:Up-Regulation
D018925:Chemokines; D019009:Proto-Oncogene Proteins c-kit