Dimethyloxaloylglycine-preconditioned Human Umbilical Cord Mesenchymal Stem Cells Protects Against Early Pregnancy Loss in Mice.

Abstract

Early pregnancy loss (EPL), a common pregnancy complication, yet has few effective preventive measures currently. To investigate whether dimethyloxaloylglycine (DMOG)-preconditioned human umbilical cord mesenchymal stem cells (hUC-MSCs) can prevent EPL, we initially evaluated the effect of DMOG on hUC-MSCs in vitro. Subsequently, the DMOG-preconditioned hUC-MSCs were transplanted into the lipopolysaccharide (LPS)-induced murine abortion model for intervention, following which we conducted phenotypic analysis. It was found that DMOG treatment enhanced the mRNA expression of Hif1α, H19, and Glut1 in hUC-MSCs and augmented their migration capability (P < 0.01). Co-culture experiments showed that DMOG-treated hUC-MSCs notably reduced the mRNA levels of Il6, Il1b, and Tnfa in LPS-induced HTR-8/SVneo cells (P < 0.01). Moreover, DMOG-preconditioned hUC-MSCs remarkably decreased the fetal resorption rate and increased the embryo weight in LPS-induced abortive mice (P < 0.01). Histological analysis indicated that DMOG-preconditioned hUC-MSCs more effectively promoted their homing and inhibited LPS-induced fibrosis at the maternal-fetal interface. Apart from suppressing inflammatory factors in the serum of pregnant mice, DMOG-preconditioned hUC-MSCs can downregulate the mRNA levels of Il2, Il1b, Tnfa, Il5, and Il9 (P < 0.01), which are pro-inflammatory cytokines secreted by M1 macrophages; and simultaneously upregulate the expression of Cd206 and Pparg (P < 0.01), which serve as the cell surface and nuclear receptors of M2 macrophages, in the embryos. Immunofluorescence further verified that the transplantation of DMOG-preconditioned hUC-MSCs could increase the expression of CD206 in embryos. Therefore, DMOG-preconditioned hUC-MSCs might prevent EPL by promoting the transformation of M1 into M2 macrophages.