ENDOCRINE DISRUPTING ENVIRONMENTAL POLLUTANS HEXACHLOROBENZENE AND CHLORPYRIFOS INDUCE ENDOMETRIOSIS ASSOCIATED ANGIOGENESIS

LEANDRO CEBALLOS; NOELIA MIRET; CAROLINA PONTILLO; LORENA ZÁRATE; MARIEL NÚÑEZ; LAURA ÁLVAREZ; ANDREA RANDI; FLORENCIA CHIAPPINI

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Fisiología y Sociedad Argentina de Inmunología

Endometriosis is a frequent and chronic illness which is defined bythe existence of endometrial tissue outside the uterus. Angiogenesis iscritical in endometriosis progression, is a complex process involving endothelialcell migration, proliferation, tube formation, and survival. Vascularendothelial growth factor (VEGF) is a powerful angiogenic factor, whichactivates downstream effectors such as ERK1/2. This signaling pathway is involvedin endothelial cell proliferation and migration. Endocrine-disrupting environmentalpollutants are thought to play a role in the development of this disease. Hexachlorobenzene(HCB) is an organochlorinated pesticide that increases microvessel density andVEGF levels in a rat endometriosis model. Chlorpyrifos (CPF) is anorganophosphate insecticide that acts as an Endocrine Disruptor. The presentstudy examined the effect of HCB and CPF on endometriosis angiogenesis invitro. T-HESCs cells (stromal endometrial cell line) were exposed to HCB(0.005, 0.05, 0.5 and 5 μM) and CPF (0.05, 0.5, 5and 50 μM) or vehicle for 48h,and the conditioned media were then used to stimulate EA.hy926 endothelialcells. The results showed that HCB (0.005, 0.05 μM) and CPF (0.5, 5, 50 μM) induced VEGF secretion (p<0.05) inT-HESCs. Moreover, theconditioned media of HCB treatment enhanced the EA.hy926cells proliferation(PCNA expression and MTT assay) (0.005-5 μM) (p<0.05), migration (scratch motility assay) (0.005-0.5 μM) (p<0.05), ERK1/2 phosphorylation(Western blot) (0.005,0.05 μM) and tube formation(tube-like structure formation in Matrigel assay);increasing total tube length(0.005 μM p<0.05; 0.5 μM p<0.01) and branching points (0.5 μM p<0.05). The results with CPF conditionedmedia showed an increase in cell migration rate (5 μM p<0.005). Our results demonstrated thatHCB and CPF exposure induces VEGF secretion in human endometrial cells triggeringangiogenesis in endothelial cells, a critical event for the endometriosisprogression.<!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073732485 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}