[Expression of CD47 and its ligands in pregnant mice infected with during pregnancy].

OBJECTIVE

To investigate the dynamic expression of cluster of differentiation 47 (CD47) and its ligands signaling regulatory protein α (SIRPα) and thrombospondin-1 (TSP-1) in mice infected with in the second and third trimesters.

METHODS

C57BL/6J mice (6 to 8 weeks old) were used for modeling infection in the first trimester, and the pregnant mice were randomly divided into the normal control and infection groups, of 10 mice in each group. Pregnant mice in the infection group were intraperitoneally injected with 150 tachyzoites on gestational day (Gd) 6.5, while pregnant mice in the normal control group were intraperitoneally injected with the same volume of physiological saline at the same time. The uterine and placental specimens were collected from all pregnant mice on Gd12.5 and Gd18.5, and the pregnant outcomes were recorded. The pathological damages of mouse uterine and placental specimens were observed using hematoxylin-eosin (HE) staining on Gd12.5 and Gd18.5. The relative expression of , , , surface antigen 1 (), interferon-γ (), interleukin-2 (), and was quantified in mouse uterine and placental specimens using real-time fluorescence quantitative PCR (qPCR) assay, and the CD47, SIRPα, TSP-1 expression was determined in mouse uterine and placental specimens using immunohistochemical staining.

RESULTS

As compared with those in the normal control group, the pregnant mice in the infection group showed back arching, bristling, trembling and listlessness during pregnancy, and several mice presented virginal bleeding and abortion. Pathological examinations showed inflammatory cell infiltration, congestion and necrosis in uterine and placental specimens of pregnant mice in the infection group, a higher abortion rate of pregnant mice was seen in the infection group than in the normal control group on Gd12.5 (χ = 20.405, < 0.001) and Gd18.5 (χ = 28.644, < 0.001). qPCR assay showed significant differences in the expression of , α, , , , , and genes in mouse placental specimens between the normal control and infection groups on Gd12.5 and Gd18.5 [' () = 37.511, 29.337, 97.343, 53.755, 67.188, 21.145, 8.658 and 13.930, all values < 0.001]. Higher , α and gene expression was quantified in mouse placental specimens in the infection group than in the normal control group on Gd12.5 (all values < 0.01), and lower , and gene expression was quantified in the infection group than in the normal control group on Gd18.5 (all values < 0.001), while higher gene expression was detected in placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both values < 0.01). In addition, higher and expression and lower and expression was detected in mouse placental specimens in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all values < 0.001), and there were significant differences in the , α, , , , , and gene expression in uterine specimens of pregnant mice between the normal control and infection groups on Gd12.5 and Gd18.5 [(' and ) = 14.951, 25.977, 18.711, 48.595, 39.318, 14.248 and 15.468, all values < 0.01], and higher and expression was detected in mouse uterine specimens in the infection group than in the control group on Gd12.5 and Gd18.5 (all values < 0.01); however, no significant difference was found in the α expression ( > 0.05). Higher expression was detected in uterine specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both values < 0.01), and higher -γ and gene expression and lower and gene expression was found in the placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all values < 0.001). Spearman correlation analysis showed that the gene expression correlated positively with ( = 0.735, < 0.05) and ( = 0.655, < 0.05) and negatively with ( = -0.689, < 0.05) and expression ( = -0.795, < 0.05) in the placental specimens of pregnant mice in the infection group on Gd12.5, and the gene expression correlated negatively with -γ ( = -0.745, < 0.05) and expression ( = -0.816, < 0.05) and positively with ( = 0.704, < 0.05) and ( = 0.802, < 0.05) in the placental specimens of pregnant mice in the infection group on Gd18.5. Immunohistochemical staining showed mild CD47, SIRPα and TSP-1 expression in uterine and placental specimens of pregnant mice in the normal control group on Gd12.5 and Gd18.5, strong CD47, SIRPα and TSP-1 expression in the placental specimens of pregnant mice in the infection group on Gd12.5 and strong CD47 and TSP-1 expression in the uterine specimens of pregnant mice in the infection group on Gd12.5.

CONCLUSIONS

infection in the first trimester may cause abnormal expression of CD47 and its ligands and in the maternal-fetal interface of pregnant mice in the second and third trimesters, which may be associated with the immune escape of at the maternal-fetal interface.