Hexachlorobenzene exposure induces pro-angiogenic microenvironment in an in vitro model of endometriosis

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

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2019

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Farmacología Exoperimental, Sociedad Argentina de Biología y Sociedad Argentina de Protozoología

Endometriosis, characterized by ectopic growthof endometrial tissue, is a common gynecological disease. The symptoms are pelvic pain andinfertility, affecting women quality of life. Angiogenesis is critical in maintenanceof endometrial lesions. Is a multistep process of new blood vessel formationthat involves the secretion of growth factors and degradation of theextracellular matrix, as well as migration, proliferation, and tube formationby endothelial cells. Vascular endothelial growth factor (VEGF) is a powerfulangiogenic factors that play an important role in endometriosis progression. Exposureto endocrine-disrupting environmental pollutants is associated with the diseaseetiology. Hexachlorobenzene (HCB) is a pesticide that induces toxicreproductive effects in laboratory animals. Previous results showed that HCB increasesthe volume of endometriotic like-lesions, microvessel density and VEGF levelsin a rat endometriosis model. The present study examined the effect of HCB onendometriosis angiogenesis in vitro. Human Endometrial Stromal cells (T-HESCs) were exposed toHCB (0.005, 0.05, 0.5 and 5 μM) or vehicle for 48 h, and the conditioned mediawere then used to stimulate EA.hy926 endothelial cells to evaluate cellproliferation (MTT assay and PCNA expression), migration (scratch motilityassay) and tube-like structure formation in a Matrigel assay. The resultsshowed that HCB (0.005-0.05 μM) induced VEGF secretion (p<0.05) in T-HESCscells. Moreover the conditioned media treatment enhanced the EA.hy926 cellsproliferation (0.005-5 μM) (p<0.05), migration (0.005-0.5 μM) (p<0.05),and tube formation 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). Our results demonstrated that HCBexposure induces angiogenic factors secretion in human endometrial cells T-HESC,triggering an increase in the ability of endothelial cells to form new vessels,a critical event for the endometriosis progression.&lt;!-- /* 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:-536870145 1107305727 0 0 415 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-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri",sans-serif;mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman";mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-fareast-font-family:Calibri;mso-hansi-font-family:Calibri;}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;}