Autoimmune thyroiditis (AIT) with euthyroid is associated with miscarriage. But the exact mechanism remains unclear. Studies have shown that the programmed cell death-1 (PD-1)/programmed cell death -ligand 1 (PD-L1) pathway is essential for normal pregnancy. However, the expression of PD-L1 in gestational trophoblasts in mice with autoimmune thyroiditis and the mechanisms leading to miscarriage have not been fully investigated. Immunofluorescence and Western blot were used to detect the expression of PD-L1, p-ERK, MMP-2 and MMP-9 in embryonic trophoblast cells of pregnant mice with AIT. The expression of PD-L1 in HTR-8/SVneo cells were silenced, and the expression of PD-L1, MMP-2, MMP-9, ERK and p-ERK1/2 was detected by Western blot analyses and immunofluorescence assays. Invasive assays were performed in PD-L1 silenced HTR-8/SVneo cells using a Transwell chamber. Compared with normal pregnancy, the expression of PD-L1, ERK, p-ERK, MMP-2 and MMP-9 in embryonic trophoblast cells was significantly lower in pregnant mice with AIT. Compared with the negative control (NC) group (cells transfected with negative control siRNA), phosphorylation of MMP-2, MMP-9 and P-ERK1/2 proteins was significantly reduced in HTR-8/SVneo cells transfected with PD-L1 siRNA, and the number of cells penetrating the membrane was reduced. AIT inhibits ERK/MMP-2 and MMP-9 pathways through PD-L1 reduction, attenuates embryonic trophoblast invasion and ultimalely induces miscarriage ultimately.

中文翻译：

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PD-L1在自身免疫性甲状腺炎中的表达减少，通过ERK / MMP途径减弱滋养细胞的侵袭

具有自身甲状腺功能的自身免疫性甲状腺炎（AIT）与流产有关。但是确切的机制仍不清楚。研究表明，程序性细胞死亡1（PD-1）/程序性细胞死亡配体1（PD-L1）途径对于正常妊娠至关重要。然而，PD-L1在自身免疫性甲状腺炎小鼠的妊娠滋养细胞中的表达及其导致流产的机制尚未得到充分研究。免疫荧光和Western blot检测PD-L1，p-ERK，MMP-2和MMP-9在AIT妊娠小鼠胚胎滋养细胞中的表达。沉默HTR-8 / SVneo细胞中PD-L1的表达，并通过Western印迹分析和免疫荧光检测法检测PD-L1，MMP-2，MMP-9，ERK和p-ERK1 / 2的表达。使用Transwell室在PD-L1沉默的HTR-8 / SVneo细胞中进行侵袭分析。与正常妊娠相比，AIT妊娠小鼠胚胎滋养层细胞中PD-L1，ERK，p-ERK，MMP-2和MMP-9的表达明显降低。与阴性对照组（NC）组相比（转染了阴性对照siRNA的细胞），在用PD-L1 siRNA转染的HTR-8 / SVneo细胞中MMP-2，MMP-9和P-ERK1 / 2蛋白的磷酸化显着降低，并减少了穿透膜的细胞数量。AIT通过降低PD-L1抑制ERK / MMP-2和MMP-9途径，减弱胚胎滋养细胞的侵袭并最终导致流产。AIT怀孕小鼠的胚胎滋养层细胞中的MMP-2和MMP-9明显降低。与阴性对照组（NC）组相比（转染了阴性对照siRNA的细胞），在用PD-L1 siRNA转染的HTR-8 / SVneo细胞中MMP-2，MMP-9和P-ERK1 / 2蛋白的磷酸化显着降低，并减少了穿透膜的细胞数量。AIT通过降低PD-L1抑制ERK / MMP-2和MMP-9途径，减弱胚胎滋养细胞的侵袭并最终导致流产。AIT怀孕小鼠的胚胎滋养层细胞中的MMP-2和MMP-9明显降低。与阴性对照组（NC）组相比（转染了阴性对照siRNA的细胞），在用PD-L1 siRNA转染的HTR-8 / SVneo细胞中MMP-2，MMP-9和P-ERK1 / 2蛋白的磷酸化显着降低，并减少了穿透膜的细胞数量。AIT通过降低PD-L1抑制ERK / MMP-2和MMP-9途径，减弱胚胎滋养细胞的侵袭并最终导致流产。