Hum. Reprod. Advance Access originally published online on May 2, 2008
Human Reproduction 2008 23(7):1614-1626; doi:10.1093/humrep/den125
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Combination of estrogen and dioxin is involved in the pathogenesis of endometriosis by promoting chemokine secretion and invasion of endometrial stromal cells
1 Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, People’s Republic of China 2 Department of Obstetrics and Gynecology, Affiliated Hospital, Hainan Medical College, Haikou 570102, People’s Republic of China
3 Correspondence address. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, People’s Republic of China. Tel/Fax: +86-21-63457331; E-mail: djli{at}shmu.edu.cn
BACKGROUND: The CC chemokines, regulated on activation, normal T-cell expressed and secreted (RANTES) and macrophage-inflammatory protein-1alpha (MIP-1
), have been identified as potential contributors to the pathogenesis and the progression of endometriosis. Dioxin, an air pollutant, and estrogen also appear to be involved in endometriosis. The aim of this study was to probe into the effect of dioxin and estrogen on expression of the chemokines in endometriosis-associated cells, and to explore the pathogenesis of endometriosis.
METHODS: Co-culture models were established to evaluate the secretion of human RANTES and MIP-1. The effects of a dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and estrogen on the invasion of endometrial stromal cells (ESC) were also examined by using an invasion assay, and the translation and proteolytic activity of matrix metalloproteinase (MMP)-9 and MMP-2 in ESC were determined by western blot and zymography, respectively.
RESULTS: Our results showed that the combination of 17β-estradiol and TCDD increased the secretion of RANTES and MIP-1, promoted the invasiveness of ESC and increased the expression of MMP-2 and MMP-9 in ESC. Anti-RANTES, anti-MIP-1 neutralizing antibody or antibody against their receptors could effectively inhibit the invasiveness of ESC and the expression of MMP-2 and MMP-9.
CONCLUSIONS: The combination of 17β-estradiol with TCDD may facilitate the onset of endometriosis and contribute to its development by increasing the invasion of ESC mediated by CC-motif chemokines.
Key words: endometriosis/air pollutant/estrogen/chemokines
Submitted on October 8, 2007; resubmitted on March 13, 2008; accepted on March 26, 2008.
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