Effect of human seminal fluid on the growth of endometrial cells of women with endometriosis.
OBJECTIVE
We investigated the effect of human seminal fluid on the growth of endometrial cells derived from women with and without endometriosis.


METHODS
Seminal plasma (SP) was collected from 18 healthy fertile men. Serum, peritoneal fluid (PF) and tissue specimens of eutopic and ectopic endometrium were collected from 45 women with endometriosis and 20 women without endometriosis during laparoscopic surgery. Prostaglandin (PG) E2, hepatocyte growth factor (HGF), and estradiol (E2) levels in each sample of SP, serum and PF were measured by enzyme-linked immunosorbent assay. The growth pattern of cells derived from eutopic and ectopic endometria in response to SP was examined by 5-bromo-2-deoxyuridine (BrdU) incorporation assay.


RESULTS
Seminal plasma was able to significantly stimulate the growth of epithelial cells and stromal cells derived from the eutopic and ectopic endometria of women with endometriosis (2-3-fold) when compared with control media. The SP-promoted proliferation of both gland cells and stromal cells derived from eutopic endometria was also remarkably higher in women with endometriosis than that of women without endometriosis. Although levels of PGE2, HGF and E2 in SP were variable when compared with other body fluids, the levels of PGE2 and HGF in SP were significantly higher than those in either peritoneal fluid or serum of women with or without endometriosis. Pretreatment of cells with individual anti-PGE2 antibody, anti-HGF antibody and two selective estrogen receptor modulators, tamoxifen and raloxifene was unable to suppress SP-mediated growth of endometrial cells. However, pretreatment of cells with combined anti-PGE2 antibody plus anti-HGF antibody or combined anti-PGE2 antibody plus anti-HGF antibody plus tamoxifen or raloxifene was able to significantly suppress SP-promoted growth of eutopic and ectopic endometrial cells.


CONCLUSIONS
Human seminal fluid enriched with different macromolecules may promote the growth of endometrial cells derived from women with endometriosis. Our findings may suggest some detrimental effect of unprotected sexual intercourse in women with endometriosis.
Khan
Khaleque N
KN
Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. nemokhan@nagasaki-u.ac.jp
Kitajima
Michio
M
Hiraki
Koichi
K
Fujishita
Akira
A
Sekine
Ichiro
I
Ishimaru
Tadayuki
T
Masuzaki
Hideaki
H
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D015232:Dinoprostone / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D012661:Semen / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D004958:Estradiol; D017228:Hepatocyte Growth Factor; D015232:Dinoprostone