Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner

Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)?Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC.The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood.The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated.DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay.DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants.Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis.The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua, a crucial process for successful pregnancy, takes place.This work was supported by the Consejeria de Economia, Innovacion y Ciencia, Junta de Andalucia (Grant CTS-6183, Proyectos de Investigacion de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Spain (Grants PS09/00339 and PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio de Educacion y Ciencia, Spain and the University of Granada. The authors have no conflict of interest.