Osteoprotegerin (OPG) Interacts with Syndecan-1 to Mediate Human Endometrial Stromal Decidualization <i>via</i> Decreasing Akt Phosphorylation

Abstract

Methods: Human endometrial tissues from proliferative stage to secretory stage of normal menstrual cycle, and decidua tissues from normal pregnancy and recurrent pregnancy loss patients were collected to analyze the expression of OPG. Human endometrial stromal cells (HESCs) and primary human endometrial stromal cells (ESCs) were performed to explore the function and mechanism of OPG during decidualization. Findings: OPG expressed in human endometrium across menstrual cycle and during the human endometrial stromal cell decidualization. Knockdown experiments revealed that decrease of OPG impaired the expression of decidual markers prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) without interference with the cell proliferation. Knockdown of OPG increased the phosphorylation of Akt and ERK1/2 during HESCs decidualization. Inhibition of PI3K signaling can rescue the impaired expression of decidual markers PRL and IGFBP-1 in response to OPG knockdown, but the ERK1/2 inhibition cannot. Further experiments revealed that OPG mediates human endometrial stromal decidualization by interacting with Syndecan-1 via decreasing Akt phosphorylation. Finally, endometrial expression of OPG was significantly lower in recurrent pregnancy loss (RPL) endometrial samples than that in normal pregnancy samples during the first trimester. Interpretation: OPG is required for decidualization, and the decrease of OPG is associated with recurrent pregnancy loss. These findings would provide a new candidate for diagnosis and treatment of infertility in women. Funding: This work was supported by the National Natural Science Foundation of China. Declaration of Interest: The authors declare that there is no conflict of interests. Ethical Approval: This study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Xiamen University and written informed consent was obtained from all participants in accordance with the guidelines in The Declaration of Helsinki 2000.