Oocyte donation (OD) pregnancies are characterized by a complete immunogenetic dissimilarity between mother and fetus, which requires enhanced immunoregulation compared to naturally conceived (NC) pregnancies. The trophoblast expresses co-inhibitory ligands crucial for regulation of the maternal T cell response. Therefore, we studied the role of placental immune checkpoint inhibitors for the establishment of fetal tolerance and their relation to the development of preeclampsia in OD compared to NC pregnancies. Placental tissue from uncomplicated OD (n = 21) and NC (n = 21) pregnancies, and OD (n = 9) and NC (n = 15) pregnancies complicated with preeclampsia were studied. Protein expression of co-inhibitory ligands PD-L1 and CD200 was double blind semi-quantitatively determined by immunohistochemistry. Messenger RNA expression of PD-L1, CD200 and indoleamine 2,3-dioxygenase (IDO) was determined using qPCR. Decreased PD-L1 and CD200 protein expression and increased IDO mRNA expression was observed in uncomplicated OD versus NC pregnancies (all p < 0.05). CD200 protein expression was positively correlated with PD-L1 expression in all groups, with the number of HLA total mismatches and with HLA class I mismatches in uncomplicated OD cases (all p < 0.05). Preeclamptic cases showed lower PD-L1 protein and CD200 protein and mRNA expression in OD compared to NC pregnancies (all p < 0.05). This study shows that signaling by co-inhibitory PD-L1 and CD200 and by immunosuppressive IDO is altered in the placenta of OD pregnancies, suggesting a contribution to the higher risk for preeclampsia. These insights provide future prospects in unraveling the immune paradox of oocyte pregnancy, which are applicable for better risk management and treatment of uncomplicated and preeclamptic pregnancies.

卵母细胞捐赠 (OD) 妊娠的特点是母亲和胎儿之间的免疫遗传学完全不同，与自然受孕 (NC) 妊娠相比，这需要增强的免疫调节。滋养层表达对调节母体 T 细胞反应至关重要的共抑制配体。因此，我们研究了胎盘免疫检查点抑制剂在建立胎儿耐受性方面的作用，以及与 NC 妊娠相比，它们与 OD 中先兆子痫发展的关系。研究了来自无并发症 OD (n = 21) 和 NC (n = 21) 妊娠以及 OD (n = 9) 和 NC (n = 15) 妊娠合并先兆子痫的胎盘组织。共抑制配体 PD-L1 和 CD200 的蛋白质表达是通过免疫组织化学双盲半定量测定的。PD-L1 的信使 RNA 表达，CD200 和吲哚胺 2,3-双加氧酶 (IDO) 使用 qPCR 测定。在无并发症的 OD 与 NC 妊娠中观察到 PD-L1 和 CD200 蛋白表达降低和 IDO mRNA 表达增加（所有 p < 0.05）。CD200 蛋白表达与所有组中的 PD-L1 表达、HLA 总错配数量和无并发症 OD 病例中的 HLA I 类错配呈正相关（所有 p < 0.05）。与 NC 妊娠相比，先兆子痫病例在 OD 中显示出较低的 PD-L1 蛋白和 CD200 蛋白和 mRNA 表达（所有 p < 0.05）。这项研究表明，共抑制 PD-L1 和 CD200 以及免疫抑制性 IDO 的信号在 OD 妊娠的胎盘中发生了改变，这表明导致先兆子痫的风险更高。