Objective: The programed cell death gene-1 ligand (PDL-1) is expressed by villous syncytiotrophoblasts, cytotrophoblasts, and fetal cells in close contact with maternal tissue and blood. Programmed cell death gene-1 (PD-1) and the PDL-1 pathway cooperate with human leucocyte antigen-G (HLA-G), expressing intermediate trophoblastic cells and syncytiotrophoblasts to inhibit the function of activated T-cells. With this mechanism, the immunosuppressive microenvironment protects the placenta. This study investigated changes in PD-1 and PD-L1 gene expression in patients with a history of recurrent pregnancy loss (RPL).
Materials and methods: Sixty patients participated in the study and were divided into three groups. Group 1 (G1): healthy pregnancy, G2: RPL but not low-molecular-weight heparin (LMWH), and G3: RPL and LMWH. PD-1 gene expression in placental tissue samples was measured by reverse-transcriptase polymerase chain reaction and PD-L1 Elisa assay, and the study was supported by histopathology.
Results: The PD-L1 value decreased significantly in G2. A significant difference was observed between the groups in PD-1 gene expression levels in G1 and G2. It was observed that vascularization increased and the villi structures intensified in G3. In G2, there was villus dysplasia in the placenta, enlargement in the intervillous region, and fibrin deposition. It was observed that the villi structures in G3 returned to a morphology similar to that of G1.
Conclusion: T-cells are activated in patients using LMWH, and a new therapeutic strategy can be developed to prevent pregnancy loss by targeting the PD-1 pathway.
Keywords: Low molecular weight heparin; placental disorders; pregnancy complications; recurrent pregnancy loss.