Involvement of ILR4α and TLR4 in miscarriages

Background: The purpose of this study was to analyze the involvement of signaling via Interleukin-4-Receptor alpha (IL4R alpha) and Toll like receptor (TLR) 4 at the fetomaternal interface in the process of early pregnancy. Patients And Methods: Placenta specimens of 46 patients in early pregnancy were analyzed (normal pregnancy (n = 15), spontaneous (n = 15) and habitual abortion (n = 16)). TLR4 and IL4R alpha were analyzed by immunohistochemistry, immunofluorescence and real time PCR. Statistical analysis was carried out using SPSS 23 and Microsoft Excel. Results: IL4R alpha could be detected in trophoblast cells of all groups. It was significantly downregulated in the syncytiotrophoblast of spontaneous and recurrent abortions (p = 0.001), and in decidual tissue of spontaneous abortions (p = 0.001). Expression of TLR4 was decreased in the intermediate villous trophoblast (IVT) and decidua of spontaneous abortions (p = 0.04 & 0.003, respectively). On mRNA level expression of IL4R alpha and TLR4 was significantly decreased in the group of recurrent miscarriages (IL4R alpha p = 0.002, TLR4 p = 0.004). Conclusion: This study contributes new findings to the understanding of the complex molecular interplay at the fetomaternal interface in normal pregnancy and miscarriages. For the first time signaling via IL4R alpha being involved at the very beginning of the generation of new life could demonstrated. Moreover, new evidence was provided regarding TLR4 playing a pivotal role in early pregnancy.