Differential infiltration of macrophages and prostaglandin production by different uterine leiomyomas.
BACKGROUND
The association between uterine myoma and infertility is still controversial. The anatomical defect of endometrium by uterine fibroids could be a factor for reducing pregnancy rates and increasing miscarriage rates. However, pregnancy and implantation rates were found to be significantly lower in women with intramural myomas (IMMs), when there was no deformity of uterine cavity. This could be due to other biological factors such as increased accumulation of inflammatory cells within fibroid tissue and corresponding endometrium that might impair fertility. Therefore, we tried to investigate the pattern of macrophage (Mvarphi) accumulation in different uterine fibroids and the production of chemokine and prostaglandin (PG) by these tissues.


METHODS
The selection criteria of uterine fibroids were based on the classification of European Society of Hysteroscopy. Biopsy specimens were collected from respective nodules and autologous endometrium of 20 women with submucosal myoma (SMM), 29 women with IMM and 18 women with subserosal myoma (SSM). CD68 immunoreactive Mvarphis were identified in these tissues by immunohistochemistry. A fraction of corresponding tissues were homogenized, and levels of monocyte chemotactic protein-1 (MCP-1) and PGF(2alpha) were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Mvarphi infiltration in the myoma nodule and corresponding endometrium of women with SMM and IMM was significantly higher than that of women with SSM or control women (P<0.01 and P<0.05, respectively). This tissue accumulation of inflammatory cells was independent of the sizes of the myoma nodules and phases of menstrual cycle. The tissue concentration of MCP-1 corresponded to increased Mvarphi infiltration and was significantly higher in women with SMM and IMM than that in women with SSM (P<0.05 for each). A positive correlation was observed between MCP-1 concentration and accumulated Mvarphi numbers in the endometrium of women with SMM and IMM but not in women with SSM. The tissue levels of PGF2alpha were also significantly higher in the nodule and corresponding endometrium of women with SMM and IMM than that in SSM or control women (P<0.05 for each).


CONCLUSIONS
Higher production of MCP-1 could be responsible for the increased accumulation of Mvarphi in women with SMM and IMM. The augmented inflammatory reaction in endometrium and increased PGF2alpha levels might be detrimental to reproductive outcome in women with SMM or IMM.
Miura
Seiyou
S
Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, and The Japanese Red Cross Nagasaki Atomic Bomb Hospital, Japan.
Khan
Khaleque Newaz
KN
Kitajima
Michio
M
Hiraki
Koichi
K
Moriyama
Shingo
S
Masuzaki
Hideaki
H
Samejima
Tetsurou
T
Fujishita
Akira
A
Ishimaru
Tadayuki
T
D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm / Q000032:analysis; D001706:Biopsy; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000032:analysis; D015237:Dinoprost / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D011453:Prostaglandins / Q000032:analysis*; D014463:Ultrasonography; D014594:Uterine Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D011453:Prostaglandins; D015237:Dinoprost