Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure

Impaired endometrial receptivity was the main cause of recurrent implantation failure (RIF); however, its underlying mechanisms had not been elucidated. This study aimed to determine the expression level of high-mobility group box protein 1 (HMGB1) in the endometrium with RIF and its effect on endometrial receptivity.

Genome-wide expression profiling, real-time reverse transcription PCR, immunohistochemical staining, western blot, and in vitro assays were performed in this study. We found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility and successfully achieve conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to that in the control group (P = 0.001), consistent with the results of the genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells dramatically displayed a marked deficiency in supporting blastocysts and human embryonic JAR cells adhesion, which mimic the process of embryo adhesion.

These findings strongly indicated that increased HMGB1 levels suppressed the epithelial cell adhesion capability, therefore contributing to impaired endometrial receptivity in patients with recurrent implantation failure, which can be used as a target for the recognition and treatment of recurrent implantation failure in clinical practice.