Role of immunoreactions and mast cells in pathogenesis of human endometriosis--morphologic study and gene expression analysis.

ABSTRACT

STUDY OBJECTIVES: 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.