Inflammosome in the human endometrium: further step in the evaluation of the ‘‘maternal side’’

Objective: To investigate the expression of inflammosome components (NALP-3, associated speck-like protein containing a CARD [ASC]) and their activation (caspase-1, interleukin [IL]-1b, and IL-18 secretion) in the human endometrium from fertile and women with history of recurrent pregnancy loss (RPL). Design: Experimental study. Setting: University hospital. Patient(s): Ten fertile women (control group [CTR]) and 30 women with RPL. Intervention(s): None. Main Outcome Measure(s): Endometrial samples were collected by hysteroscopy during the putative window of implantation and evaluated for chronic endometrial inflammation by hystopathological analysis. Inflammosome expression was analysed by immunohystochemical staining (27 RPL and 10 CTR women). The expression of NALP-3 and ASC protein was quantified by Western blot (30 RPL and 10 CTR women). Caspase-1 activation and IL-1b and IL-18 secretion was quantified by ELISA (30 RPL and 10 CTR women). Result(s): We observed a significantly increased expression of inflammasome NALP-3 and ASC protein, an increased activation of caspase-1, and increased levels of IL-1b and IL-18 in RPL endometrium compared with CTR. Conclusion(s): Abnormal activation of endometrial innate immunity by means of inflammosome, stimulated by pathogen- or damage-associated molecular patterns, may represent an additional mechanism, currently not investigated, negatively interfering with endometrial receptivity. More studies are required [1] to identify the primary trigger of endometrial inflammosome activation and its clinical impact in the occurrence of RPL; and [2] to validate the inflammosome components as a novel family of endometrial biomarkers and promising therapeutic targets in RPL.