The endometria of women with endometriosis exhibit dysfunctional expression of complement regulatory proteins during the mid secretory phase

The control of complement activation within embryo-endometrium environment is critical for embryo survival. Cell evasion from complement attack requires interaction of complement regulatory proteins (CRPs) with cell adhesion alpha v beta 3 integrin. We aim to compare the expression of CRPs in endometria of women with and without endometriosis and to examine the molecular interaction of decay accelerating factor (DAF) with alpha v beta 3 integrin. Endometrial expression of Membrane cofactor protein (CD46), Decay accelerating factor (DAF), Membrane attack complex inhibitory factor (CD59) and beta 3 integrin subunit were determined through menstrual cycle by immunohistochemistry. DAF protein quantity was determined by Western blot and mRNA levels measured in epithelial cells isolated by laser capture microdissection (LCM). Using in vitro assay, we examined DAF and beta 3 integrin expression through paracrine regulation between endometrial compartments. To determine whether beta 3 integrin and DAF interacts in vivo, endometrial samples were subjected to immunoprecipitation and colocalization using dual immunofluorescence technique. DAF and beta 3 integrin expression were significantly low in samples from women with endometriosis during mid secretory phase. This observation was supported by decreased DAF protein quantity; faint DAF and beta 3 integrin interaction and reduced mRNA levels in cells dissected by LCM. Moreover epithelial DAF and beta 3 integrin expression through paracrine regulation by progesterone from stromal compartment was disrupted in endometriosis. Endometria from women with endometriosis exhibits aberrant expression of complement proteins. The abnormal DAF expression potentially compromises embryo survival, contributing to understand the implantation failure in women with endometriosis.Fondo Nacional de Desarrollo Cientifico y Tecnologico, FONDECYT, Chile 1140688 Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health R01HD067721 Canadian Institutes of Health Research Fogarty International Fellowship Awar