Preliminary Study On The Pathogenesis Of OX40-OX40L And PD-1-PD-L1 Signaling Molecules In Unexplained Recurrent Spontaneous Abortion

Objective:To study the expression of OX40-OX40L and PD-1-PD-L1 signaling molecules in the decidua of patients with unexplained recurrent spontaneous abortion(URSA)To investigate the pathogenesis of OX40-OX40L and PD-1-PD-L1 signaling molecules in the abnormal decidualization of recurrent spontaneous abortion and the abnormal interaction between immune cells and decidual cells.Methods:Collection of 20 cases of URSA cases and normal pregnancy(NP)cases who voluntarily terminated a pregnancy at a family planning clinic from May 2018 to September 2018 in the Second Affiliated Hospital of Suzhou University,(reverse transcription-polymerase chain reaction)were used to detect the expression levels of OX40,OX40L,PD-1 and PD-L1 in the aborated decidual tissue of the two groups.HE(hematoxylin-eosin)staining was used to observe the pathological changes of decidual tissue in the two groups.The expression and localization of OX40,OX40L,PD-1 and PD-L1 in decidual tissue of the two groups were detected by immunohistochemistry.Immunofluorescence double staining was used to investigate the expression of OX40 and PD-1 on CD3+T cells in decidua of both groups and the expression of OX40L and PD-L1 on decidual cells.Compare the differences using statistical methods such as T test and Fisher exact probability method.Results:1.The relative expression of mRNA of each signal molecule was detected by real-time PCR:In the URSA and NP group,the relative expression of OX40L mRNA was increased in the decidua of URSA patients compared with NP group,and the difference between the two groups was statistically significant(P<0.05).There was no significant difference in the relative expression of OX40,PD-1 and PD-L1 between the URSA and NP groups(P>0.05).2.HE staining showed that compared with normal pregnancy,decidual cells in the decidual tissue of URSA patients were loosely connected and interstitial edema.Immunohistochemistry showed that the expression of PD-L1 in decidual tissue of patients with URSA was significantly lower than that of normal pregnancy(P<0.05);the expression of OX40L was significantly higher than that of normal pregnancy(P<0.05).There was no significant difference in the expression of PD-1 and OX40(P>0.05).3.In decidual tissue of URSA patients,the fluorescence intensity of OX40L on decidual cells was much greater than that of normal pregnancy(P<0.05).The fluorescence intensity of PD-L1 on decidual cells was much smaller than that of normal pregnancy(P<0.05).There was no significant difference in the fluorescence intensity of PD-1 and OX40 on CD3+T cells(P>0.05).Conclusions:1.Increased expression of OX40L and decreased expression of PD-L1 in decidual tissue of patients with unexplained recurrent spontaneous abortion suggests that OX40L and PD-L1 expression is associated with abortion in patients with unexplained recurrent spontaneous abortion.2.There was no significant difference in the expression of OX40 and PD-1 on T lymphocytes in the decidual tissue of patients with unexplained recurrent spontaneous abortion.However,the expression of OX40L and the expression of PD-L1 were decreased in decidual stromal cells.Abnormal expression of costimulatory molecules in decidual stromal cells,which suggests that the regulation of the interaction between T lymphocytes and decidual stromal cells may be the pathogenesis of unexplained recurrent spontaneous abortion.