Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Eur J Obstet Gynecol Reprod Biol. 2010 Apr;149(2):204-9. doi: 10.1016/j.ejogrb.2009.12.022. Epub 2010 Jan 25.
We investigated the effect of human seminal fluid on the growth of endometrial cells derived from women with and without endometriosis.
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.
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.
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.
研究人精液对子宫内膜异位症和非子宫内膜异位症患者在位和异位子宫内膜细胞生长的影响。
从 18 名健康的生育期男性中收集精液。在腹腔镜手术中,从 45 名子宫内膜异位症患者和 20 名非子宫内膜异位症患者中收集血清、腹腔液(PF)和组织标本。通过酶联免疫吸附试验(ELISA)检测 SP、血清和 PF 中各样本的前列腺素(PG)E2、肝细胞生长因子(HGF)和雌二醇(E2)水平。通过 5-溴-2-脱氧尿苷(BrdU)掺入试验检测 SP 对来源于子宫内膜异位症患者在位和异位子宫内膜的细胞生长模式的影响。
与对照培养基相比,精液能显著刺激子宫内膜异位症患者在位和异位子宫内膜上皮细胞和基质细胞的生长(2-3 倍)。子宫内膜异位症患者在位子宫内膜来源的腺体细胞和基质细胞的 SP 促进增殖也明显高于非子宫内膜异位症患者。虽然与其他体液相比,SP 中的 PGE2、HGF 和 E2 水平变化较大,但 SP 中的 PGE2 和 HGF 水平明显高于子宫内膜异位症或非子宫内膜异位症患者的腹腔液或血清中的水平。用单克隆抗 PGE2 抗体、抗 HGF 抗体和两种选择性雌激素受体调节剂他莫昔芬和雷洛昔芬预处理细胞,不能抑制 SP 介导的子宫内膜细胞生长。然而,用联合抗 PGE2 抗体加抗 HGF 抗体或联合抗 PGE2 抗体加抗 HGF 抗体加他莫昔芬或雷洛昔芬预处理细胞,能显著抑制 SP 促进的在位和异位子宫内膜细胞生长。
富含不同大分子的人精液可能促进子宫内膜异位症患者在位和异位子宫内膜细胞的生长。我们的发现可能提示了未受保护的性行为对子宫内膜异位症患者的一些有害影响。