The endocrine disruptor hexachlorobenzene induces cell migration and enhances aromatase expression levels in human endometrial stromal cells.

CHIAPPINI F; CEBALLOS; PONTILLO C; MIRET N; FARINA MG; A. RANDI

Congreso; XIV International Congress of Toxicology; 2016

Introduction: Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Hexachlorobenzene (HCB) is a pesticide that induces toxic reproductive effects in laboratory animals. Endometriosis is characterized by the presence of endometrial tissues outside the uterine and is a major cause of infertility in women. Aromatase transforms androgen to estrogen, and its expression is increased in eutopic and ectopic endometrial of women with endometriosis. Aromatase expression in endometriosis cells is induced via cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) pathway. The finding that estradiol (E2) stimulates COX-2 expression suggests that E2 and COX-2 exist in a positive feedback loop. Biological effects of E2 are mediated through two functional estrogen receptors (ER), ERα and ERβ. ERα is the major mediator of estrogenic effects on stimulation of proliferation and induction of progesterone receptor (PR) expression. PRA and PRB serve an anti-inflammatory role in the uterus by antagonizing COX-2 expression. Degradation of extracellular matrix by metalloproteinases is a basic step in the migration and invasiveness in endometriosis. Recent studies from our laboratory have demonstrated that HCB enhances COX-2 expression, metalloproteinase 2 and 9 activation and PGE2 secretion in human endometrial stromal cells.Objective: Our aim was to investigate the HCB effect in human endometrial stromal cell line T-HESC on: a) cell migration (scratch motility assay), b) aromatase expression (Western Blot), c) estrogen receptor and d) progesterone receptor protein levels (Western Blot). Materials and Methods: T-HESC cells were exposed to HCB (0.005, 0.05, 0.5 and 5 μM) or vehicle for 24 hours. Results: The results showed that the pesticide increases the cell migration ratio (47%, p