Endocrine disruptor hexachlorobenzene induces cell migration and invasion, and enhances aromatase expression levels in human endometrial stromal cells

CHIAPPINI F; CEBALLOS L; OLIVARES C; BASTON JI; MIRET N; PONTILLO C; ZARATE L; SINGLA JJ; FARINA M; MERESMAN G; RANDI A

FOOD AND CHEMICAL TOXICOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2022 vol. 162

0278-6915

Endometriosis is the presence and growth of endometrial tissue outside of the uterus.Previous studies have suggested that endocrine disrupting chemicals such as organochlorinepesticides could be a risk factor for endometriosis. Hexachlorobenzene (HCB) is a weak ligandof the aryl hydrocarbon receptor (AhR) and promotes metalloproteinase and cyclooxygenase-2 (COX-2) expression, as well as, c-Src activation in human endometrial stromal cells (T-HESC)and in rat endometriosis model. Our aim was to evaluate the effect of HCB exposure onoestrogen receptor (ER) ɑ and β, progesterone receptor (PR) and aromatase expression, aswell as, on cell migration and invasion in T-HESC and primary cultures of endometrial stromalcells from eutopic endometria of control subjects (ESC). Results show that HCB increases ERɑand aromatase protein levels and reduces PR content in both T-HESC and ESC. However, thepesticide only increases ERβ expression in ESC, without changes in T-HESC. Moreover, cellmigration and invasion are promoted by pesticide exposure involving the AhR, c-Src, COX-2and ER pathways in T-HESC. HCB also triggers ERɑ activation via phosphorylation in Y537through AhR/c-Src pathway. Our results provide experimental evidence that HCB inducesalterations associated with endometriosis, suggesting that these mechanisms couldcontribute to pesticide exposure-induced endometriosis development.