Hexachlorobenzene exposure enhances COX-2 expression and metalloprotease activities in human endometrial stromal cells.

CHIAPPINI F; BASTON JI; VACCAREZZA A; SINGLA JJ; PONTILLO C; MERESMAN G; RANDI A

Edinburgo

Congreso; Proceedings Eurotox 2014: 50th Congress of The European Societies of Toxicology.; 2014

Endometriosis is a gynecologic disorder characterized by the presence and growth of endometrialtissue in ectopic sites, causing infertility in reproductive-aged women. Evidence has emergedregarding the relation between organochlorine pollutants and endometriosis. Hexachlorobenzene(HCB) is a widely distributed pesticide that induces toxic reproductive effects and is an endocrinedisruptor. Cyclooxygenase-2 (COX-2) is involved in pathogenesis of endometriosis. Its inhibitionsuppresses activity of metalloproteases (MMPs), decreasing invasion of human endometrioticepithelial and stromal cells. Altered patterns of MMPs have been reported in endometrial tissuesfrom patients with endometriosis, suggesting that MMPs play critical roles in endometriosisdevelopment. In the present study, we examined the HCB action on MMP2 and MMP9 expression and activities, and COX-2 protein levels in HUF cells, T-HESC cells, and human endometrial stromal primary cultures. Cells were exposure to HCB (0.005, 0.05, 0.5 and 5 μM) during 3 and 24 hs, and protein levels were analyzed by Western Blotting, and MMPs activities by gel zymography. In HUF and T-HESC cells, HCB 0.5 μM increases: a)MMP9 activity (80%,p<0.01), MMP9 expression (53%,p<0.05) and MMP2 activity (53%,p<0.05) at 24 hs; b)COX-2 levels (125%,p<0.05) at 3 hs. In endometrial stromal primary cultures derived from control patients, HCB 0.05 μM enhances: a)MMP9-MMP2 activities (100,145%,p<0.05) and expression (690,191%,p<0.01); b)COX-2 levels (303%,p<0.05). However, the pesticide has a lower effect in endometrial stromal primary cultures derived from patients with endometriosis, showing a moderate increase in MMP9 and MMP2 expression and activities. In conclusion, our results shown that HCB could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.