Hexachlorobenzene exposure induces cell migration and invasion through AhR, COX-2, ER and c-Src in human endometrial stromal cells

FLORENCIA CHIAPPINI; LEANDRO CEBALLOS; CAROLINA PONTILLO; NOELIA MIRET; MARIEL NÚÑEZ; LAURA ALVAREZ; MARIANA FARINA; ANDREA RANDI

Bruselas

Congreso; 54th Congress of the European Societies of Toxicology (EUROTOX 2018); 2018

Sociedades Europeas de Toxicología

Endometriosis is characterized by the implantation of ectopic endometrial tissue outside of the uterine cavity. Is a benign gynecological disease that shares some characteristics with malignancy like migration and invasion. Although the pathophysiology is unknown, endometriosis is likely multifactorial involving interplay between genetic predisposition and environmental conditions leading to the pathogenesis. Exposure to endocrine-disrupting environmental pollutants could play a role in the disease etiology. Hexachlorobenzene (HCB) is an organochlorine pesticide found in maternal milk and in lipid foods, that induces toxic reproductive effects in laboratory animals. Recently, we demonstrated that HCB enhances cyclooxygenase-2 (COX-2) expression, metalloproteinases (MMP) 2 and 9 activation and prostaglandin E2 (PGE2) secretion in human endometrial stromal cell line T-HESC. Pathological angiogenesis is the hallmark of endometriosis. Endometriotic growth is supported by the local hormonal and inflammatory microenvironment. The present study examined the effect of HCB in T-HESC on cell migration (scratch motility assay), cell invasion (transwell invasion assay), and expression of angiogenic factor Vascular Endothelial Growth Factor (VEGF) (Western Blot). Cells were exposed to HCB (0.005, 0.05, 0.5 and 5 μM) or vehicle for 24, 48 or 72 h. Results showed that the pesticide increases cell migration (47%; 81%, 77% and 96%, p