P-313 Dysregulation of endometrial stromal serotonin homeostasis impairs decidualization in patients with recurrent implantation failure via phosphatidylcholine metabolism

Abstract

Abstract Study question Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)? Summary answer Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased expression of monoamine oxidase (MAO), affects decidualization of endometrial stromal cells. What is known already Previous studies have found that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and the mechanism remains unclear. Study design, size, duration Endometrial samples from 31 patients with RIF and 31 fertile patients were used to investigate the expression levels of MAOA, MAOB, and serotonin. We isolated human endometrial stromal cells to investigate the role of MAOA, MAOB and serotonin in inducing decidualization in vitro and further explored the mechanism using RNA-seq and LC/MS analyses. Participants/materials, setting, methods The levels of serotonin in the endometrium of patients with RIF were detected by ELISA and immunohistofluorescence, and the key genes of abnormal serotonin metabolism were analyzed combined with single-cell sequencing data. The effects of MAO on the decidualization of stromal cells were investigated using human endometrial stromal cells in vitro induced decidualization model and mouse artificially induced decidualization model. The potential mechanisms of MAO regulating decidualization were explored by RNA-seq and LC/MS analysis. Main results and the role of chance We found that women with RIF have abnormal serotonin metabolism in the endometrium and attenuated MAO in endometrial stromal cells. Endometrial decidualization was accompanied by increased MAO in vivo and in vitro. Attenuated MAO caused increased local serotonin content in the endometrium, impairing stromal cell decidualization. RNA-seq and LC/MS analyses showed that abnormal lipid metabolism, especially phosphatidylcholine metabolism, was involved in MAO-deficiency induced defective decidualization. Furthermore, decidualization defects were rescued by phosphatidylcholine supplementation. Limitations, reasons for caution This study found that impaired serotonin metabolic homeostasis and abnormally reduced MAO expression were one of the reasons for repeated implantation failure. However, the source and other potential function of serotonin in the endometrium remain to be further explored. Wider implications of the findings This study shows new insights into the mechanisms of serotonin homeostasis in human endometrial decidualization and provides new biomarkers or targets for the treatment of patients with RIF. Trial registration number not applicable