Effect Of IDO Gene On Pregnancy In Mice With Recurrent Spontaneous Abortion And Its Mechanism

Problem: To investigate the effect of the IDO(indoleamine2,3-dioxygenase)gene on pregnancy outcome in mice with recurrent spontaneous abortion(RSA)and its mechanism of action in the maternal–fetal interface.Method of study: The RSA model was established via natural mating of female CBA/J mice with male DBA/2 mice;thereafter,the female mice were randomly divided into LV-EGFP(enhanced green fluorescent protein)-IDO(lentivirus vector carrying IDO-EGFP gene),LV-EGFP(negative control lentivirus vector),and control(phosphate-buffered saline)groups,each group of 15.Ten CBA/J pregnant mice were sacrificed at 13.5 days of pregnancy,and the embryo absorption rate was determined.The number of surviving pups was calculated in each group of CBA / J mice postpartum.The average number of pups per litter,the length of the pups after birth and the growth curve of body weight.Placental and decidual tissue IDO expression was detected using immunofluorescence and western blotting.Peripheral blood regulatory T cells(Tregs)from the pregnant mice were detected using flow cytometry.Inflammatory cell infiltration in the placental and decidual tissue was observed using hematoxylin–eosin(HE)staining.Results: The LV-EGFP-IDO group had a significantly lower embryo absorption rate than the control and LV-EGFP groups(p= 0.0006,p = 0.0049,respectively)and constituted more live newborn mice,and the number of live births per fetus was significantly higher than that of the control and LV-EGPF group.The LV-EGFP-IDO group had significantly higher placental and decidual IDO protein levels than the control and LV-EGFP groups(P < 0.005),The LV-EGFP-IDO grop significantly more Tregs than the control and LV-EGFP groups(p=0.0151,p=0.0392,respectively).Placental and decidual IDO protein levels correlated positively with peripheral blood Treg expression levels.And the LV-EGFP-IDO grop significantly less inflammatorycell infiltration than the control and LV-EGFP groups.Conclusion: IDO gene may improve the pregnancy outcome of recurrent abortion mice by upregulation of regulatory T cells and reduction of inflammatory response.