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

Endometriosis is the presence and growth of endometrial tissue outside of the uterus. Previous studies have suggested that endocrine disrupting chemicals such as organochlorine pesticides could be a risk factor for endometriosis. Hexachlorobenzene (HCB) is a weak ligand of 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 on oestrogen receptor (ER) alpha and beta, progesterone receptor (PR) and aromatase expression, as well as, on cell migration and invasion in T-HESC and primary cultures of endometrial stromal cells from eutopic endometria of control subjects (ESC). Results show that HCB increases ERalpha and aromatase protein levels and reduces PR content in both T-HESC and ESC. However, the pesticide only increases ER beta expression in ESC, without changes in THESC. 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 ERalpha activation via phosphorylation in Y537 through AhR/c-Src pathway. Our results provide experimental evidence that HCB induces alterations associated with endometriosis, suggesting that these mechanisms could contribute to pesticide exposure-induced endometriosis development.

Automated summary

This study found that hexachlorobenzene (HCB) exposure can induce changes associated with endometriosis, including increased levels of estrogen receptor α and aromatase protein, decreased progesterone receptor content, and promoted cell migration and invasion. These results reveal the mechanisms by which pesticide exposure may contribute to the development of endometriosis.