Hexachlorobenzene and chlorpyrifos, environmental pollutants that disrupt the endocrine system, promote angiogenesis associated with endometriosis.

Endometriosis defined by the growth of endometrial tissues outside the uterus, affects women of reproductive age. A critical process in endometriosis progression, angiogenesis involves endothelial cell migration, proliferation and tube formation, with vascular endothelial growth factor (VEGF) playing a powerful role. Exposure to endocrine-disrupting pollutants, like Hexachlorobenzene (HCB) andChlorpyrifos (CPF), is linked to a higher risk of reproductive diseases including endometriosis. Both HCB and CPF are weak aryl hydrocarbon receptor (AhR) ligands. These study examined HCB and CPF mechanisms of action in endometriosis-associated angiogenesis in vitro. Our results show that HCB (0.005, 0.05 and 5 μM) and CPF (0.5-50 μM) induced VEGF secretion in human stromal endometrial cells (T-HESCs). Moreover, HCB- or CPF-conditioned media (HCB-CM, CPF-CM) from T-HESCs boosted endothelial cell (EA.hy926) proliferation and survival. In addition, wound healing assays rendered an increase in EA.hy926 cell migration after exposure to HCB-CM (0.005-0.5 μM) or CPF-CM (5 μM), while tube-like structures revealed an increase in neovasculogenesis after HCB-CM (0.5 μM) or CPF-CM (5 μM). Our findings show that HCB- and CPF-induced angiogenesis was mediated by AhR and VEGF receptor-2. These results demonstrate that both pesticides increase VEGF secretion in endometrial cells and triggers angiogenesis, a critical event in endometriosis progression.