Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

Abstract

High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), β2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, β2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.

Prophylaxis of decidual CD68+/CD163+ macrophage disbalance in extracorporeal fertilized women

“…Thus, the combination of progesterone and vitamin D3 may have a synergistic effect on stimulating the polarization of macrophages towards the predominance of the M 2 phenotype. Similar results were obtained by Chen Y. et al when studying the effect of the progesterone-vitamin D3 complex on the immunological status and pregnancy outcomes in rats with an autoimmune model of spontaneous abortions [ 38 ].…”

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

“…RSM accounts for approximately 2–5% of the total pregnancies [ 2 ]. Although concentrated research has identified numerous causes of RSM, such as chromosomal abnormalities, abnormal reproductive structure, endocrinopathies, and thrombophilic disorders, 50% of RSM cases are still unexplained [ 3 ]. Exploring the pathogenesis of unexplained RSM and providing early intervention are critical for ensuring a better pregnancy outcome.…”

Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis

“…Further, PRG switches the immune reaction from pro-inflammatory to antiinflammatory, facilitating Treg cell differentiation and the downregulation of IFN-γ generated by natural killer (NK) cells [20]. Based on its neuroprotective and anti-inflammatory functions, PRG is considered a drug candidate for the treatment of various inflammatory and autoimmune diseases [21][22][23][24]. Treatment with PRG can reduce the signs of EAU in mice, decrease IL-17 levels, and increase IL-10 levels [22].…”