Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Immunology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran.
Reprod Sci. 2023 Apr;30(4):1217-1228. doi: 10.1007/s43032-022-00995-y. Epub 2022 Jul 18.
Recurrent spontaneous abortion (RSA) is one of the major pregnancy-related complications. The roles of different immune cells have been studied in pregnancy complications. The current study aimed to investigate myeloid-derived suppressor cells (MDSCs) in a murine abortion model and introduce a therapeutic approach by using in vitro-generated MDSCs in this model. CBA/J × DBA/2 (abortion prone) and CBA/J × Balb/C (normal pregnancy) mice were used. The frequency of granulocytic MDSCs, monocytic MDSCs, and Tregs was checked in the bone marrow and uteroplacental tissue of mice on three gestational days (gd9.5, gd13.5, and gd17.5) using the flow cytometry approach. MDSCs were generated in vitro from bone marrow-isolated cells using GM-CSF and IL-6 cytokines. Abortion-prone mice were injected intravenously with in vitro-generated MDSCs at gd0.5, and pregnancy outcomes were recorded in treated mice. The frequency of G-MDSCs and M-MDSCs in the bone marrow of abortion-prone mice was decreased at gd9.5 (p = 0.026 and p = 0.05, respectively). In uteroplacental tissue, the frequency of G-MDSCs was significantly lower at gd9.5 and gd13.5 (p = 0.001, p = 0.029, respectively), while M-MDSCs only showed decreased number at gd9.5 (p = 0.05) in abortion-prone mice. Injection of in vitro-generated MDSCs resulted in the increased fetus and placenta weights (p = 0.049 and p = 0.012, respectively) but showed no effect on the number of live fetuses and abortion rate. The reduced frequency of both G-MDSCs and M-MDSCs in the bone marrow and at the feto-maternal interface is associated with pregnancy complications. In vitro-generated MDSCs could be considered as a potential approach to reduce these complications.
复发性自然流产（RSA）是与妊娠相关的主要并发症之一。不同免疫细胞在妊娠并发症中的作用已被研究。本研究旨在探讨鼠流产模型中的髓源性抑制细胞（MDSC），并在该模型中引入体外生成 MDSC 的治疗方法。使用 CBA/J×DBA/2（易流产）和 CBA/J×Balb/C（正常妊娠）小鼠。使用流式细胞术在妊娠第 3 天（gd9.5、gd13.5 和 gd17.5）检查骨髓和胎盘中粒细胞 MDSC、单核细胞 MDSC 和 Treg 的频率。从骨髓分离细胞中使用 GM-CSF 和 IL-6 细胞因子体外生成 MDSC。在 gd0.5 时将体外生成的 MDSC 静脉注射给易流产的小鼠，并记录治疗小鼠的妊娠结局。易流产小鼠骨髓中 G-MDSC 和 M-MDSC 的频率在 gd9.5 时降低（p=0.026 和 p=0.05）。在胎盘中，G-MDSC 的频率在 gd9.5 和 gd13.5 时明显降低（p=0.001，p=0.029），而 M-MDSC 仅在 gd9.5 时数量减少（p=0.05）。注射体外生成的 MDSC 导致胎儿和胎盘重量增加（p=0.049 和 p=0.012），但对活胎数量和流产率没有影响。骨髓和胎盘中 G-MDSC 和 M-MDSC 的频率降低与妊娠并发症有关。体外生成的 MDSC 可被视为减少这些并发症的一种潜在方法。
