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

FLORENCIA CHIAPPINI; LEANDRO CEBALLOS; CARLA OLIVARES; JUAN IGNACIO BASTÓN; NOELIA MIRET; CAROLINA PONTILLO; LORENA ZÁRATE; JOSÈ JAVIER SINGLA; MARIANA FARINA; GABRIELA MERESMAN; ANDREA RANDI

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 havesuggested that endocrine disrupting chemicals such as organochlorine pesticides could be a risk factor forendometriosis. Hexachlorobenzene (HCB) is a weak ligand of the aryl hydrocarbon receptor (AhR) and promotesmetalloproteinase and cyclooxygenase-2 (COX-2) expression, as well as, c-Src activation in human endometrialstromal 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, as well as, on cellmigration and invasion in T-HESC and primary cultures of endometrial stromal cells from eutopic endometria ofcontrol subjects (ESC). Results show that HCB increases ERɑ and aromatase protein levels and reduces PR contentin both T-HESC and ESC. However, the pesticide only increases ERβ expression in ESC, without changes in T-HESC. Moreover, cell migration and invasion are promoted by pesticide exposure involving the AhR, c-Src, COX-2 and ER pathways in T-HESC. HCB also triggers ERɑ activation via phosphorylation in Y537 through AhR/c-Srcpathway. Our results provide experimental evidence that HCB induces alterations associated with endometriosis,suggesting that these mechanisms could contribute to pesticide exposure-induced endometriosis development.