Effects Of Selective Immune Modulators On The Pregnancy In Abortive Model Mice

ObjectivesTo investigate whether HCG-derived oligopeptide MTRV (Met-Thr-Arg-Val) can prevent Poly (I:C)-induced embryo-resorption and its possible immunological mechanisms, induced embryo resorption model was established by peritoneal injection of Poly I:C to female mice in the BALB/c×C57BL/6 mating combination. To investigate the relationship between the status of galectin-1 and correlated cytokine (IL-4, IL-10, IFN-γ, TGF-βand CD25) expression and murine spontaneous abortion.Materials and MethodsThe administration of MTRV was performed at time points during pregnancy in the Poly (I:C)-induced female mice. The fetal resorption rate was measured on day 9.5 and day 13.5 of gestation. Meanwhile, the percentage of TLR3+, CD80+, IFN-γ+ and TGF-(3+ cells among CD45+ cells was tested in uterine immune cells using flow cytometry.Magnetic affinity cell sorting was performed to isolate uterine natural killer (NK) cells, and flow cytometry was performed to detect the status of galectin-1 and correlated cytokine (IL-4, IL-10, IFN-γ, TGF-βand CD25) expression in NK cells. The resorption rate of embryos and the proportion of NK cells that produce the above-mentioned molecules were compared between CBA/J×DBA/2J and CBA/J×BALB/c mice at day 12.5 of gestation.ResultsThe research showed that the multiple administrations of MTRV could not change Poly (I:C)-induced increase of the relative number of TLR3+ and CD80+ cells. However, it could abrogate the Poly (I:C)-induced increase of IFN-γ+ cells and the decrease of TGF-β+ cell number among CD45+ cells, and inhibit Poly (I:C)-induced increase of embryo-resorption.It was demonstrated that the resorption rate in CBA/J×DBA/2J mice was significantly higher than CBA/J×BALB/c mice (19.8% versus 7.3%, P＜0.01), whereas the IL-4+, IL-10+ and TGF-(3+ NK cell percentages in CBA/J×DBA/2J mice were significantly lower than CBA/J×BALB/c mice (3.93%±0.17% versus 8.23%±0.30% for IL-4,1.70%±0.16% versus 3.93%±0.20% for IL-10,12.60%±0.39% versus 16.50%±0.38% for TGF-βrespectively, P<0.01 for both). Further detection shows that the IFN-y+ and galectin-1+ NK cell percentages in CBA/J×DBA/2J mice were higher than CBA/J×BALB/c mice(2.10%±0.14% versus 1.23%±0.22% for IFN-y,P<0.01; 71.00%±1.64% versus 66.53%±1.55% for galectin-1, P＜0.05).ConclusionsThe research suggests that HCG-derived oligo peptide MTRV may modulate the functional status of cytokine production at the feto-maternal interface and subsequently inhibit Poly (I:C)-induced embryo-resorption.Taken together, it suggests that the sufficiency of IL-4+, IL-10+ and TGF-β+ NK cells and increase of the relative number of IFN-y+ and galectin-1+ NK cells in CBA/J×DBA/2J model may be correlated with its increased occurrence of embryo resorption. From another aspect, it also demonstrates the immune regulative function of galectin-1.