Dysregulation of endometrial stromal serotonin homeostasis impairs decidualization in recurrent implantation failure via phosphatidylcholine metabolism. Homo sapiens

Female infertility is associated with psychological stress. The local content of neurotransmitters in the endometrium interferes with the normal function of the endometrium. However, the specific mechanism of stress-induced fertility disorders is still unclear. Here, we revealed that disruption of endometrial stromal serotonin homeostasis controlled by monoamine oxidase (MAO) impairs decidualization in recurrent implantation failure (RIF) via lipid metabolism. We found that women with RIF have abnormal serotonin metabolic status in the endometrium and attenuated MAO in endometrial stromal cells. Endometrial decidualization was accompanied by an increase in 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, defective decidualization was rescued by phosphatidylcholine supplementation. Our results suggest that local serotonin homeostasis and appropriate MAO are critical for endometrial decidualization.