Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Department of Ultrasound, Fujian Provincial Maternal and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Braz J Med Biol Res. 2021 Jun 14;54(9):e9570. doi: 10.1590/1414-431X2020e9570. eCollection 2021.
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.
高比例表达 DX5+/CD25+/FOXP3+/CD45+/CD4+的胎盘淋巴细胞有利于维持免疫耐受，改善妊娠结局。本研究旨在比较和评估阿司匹林、维生素 D3（VitD3）和孕酮对自身免疫性复发性自然流产（RSA）模型的治疗效果。构建自身免疫性 RSA 小鼠模型，计算各组胚胎丢失率。然后分离原代小鼠胎盘淋巴细胞，通过流式细胞术检测 DX5+/CD25+/FOXP3+/CD45+/CD4+的表达。采用 ELISA 法检测抗心磷脂抗体（ACA）、β2-GP1、CXCL6、IFN-γ和 IL-6 的血清水平，评价 Th1 和 Th2 细胞的比例。自身免疫性 RSA 显著增加胚胎丢失率，阿司匹林、VitD3 和孕酮治疗可改善该模型，且孕酮治疗效果最佳。VitD3 和孕酮组的 DX5+/CD25+/FOXP3+/CD45+/CD4+阳性表达明显高于自身免疫性 RSA 组，且孕酮组表达最高。在自身免疫性 RSA 小鼠的血浆中，ACA、β2-GP1、CXCL6 和 IFN-γ 水平明显升高，IL-6 水平低于对照组。阿司匹林和孕酮治疗可逆转所有这些变化。总之，阿司匹林、VitD3 和孕酮通过调节 Th1/Th2 平衡和细胞因子改善自身免疫性 RSA 小鼠的妊娠结局，且孕酮的治疗效果最佳。
