Department of Pathology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2024 Mar 23;51(1):442. doi: 10.1007/s11033-024-09370-3.
Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study.
Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002).
Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.
在典型妊娠的三个孕期中，我们研究了 miRNA 和耗尽的 T 淋巴细胞的表达变化。
本研究纳入了 50 名健康受试者。使用流式细胞术测量分离的 PBMC 中耗尽的 T 淋巴细胞的频率。使用 qRT-PCR 评估 PD-1、TIM-3 和相关 miRNA 基因表达。分析显示，RPL 女性 PBMC 中的 PD-1 和 Tim-3 表达显著下降（p=0.0003 和 p=0.001）。此外，与健康孕妇的第一孕期相比，第二孕期 PD-1 和 TIM-3 的表达显著增加（p<0.0001 和 p=0.0002）。与第一和第二孕期相比，第三孕期 PD-1 和 TIM-3 的表达下调。在本研究中，我们证明了与第一和第三孕期相比，第二孕期女性循环中 TIM-3+/CD4+、TIM-3+/CD8+、PD-1+/CD4+和 PD-1+/CD8+耗尽的 T 淋巴细胞增加。在第三孕期，miR-16-5p 的表达显著增加（p<0.0001）。与第一孕期相比，第二（p<0.0001）和第三（p=0.0007）孕期的 miR-125a-3p 表达下调和上调。与孕妇的第一孕期相比，本研究显示第三孕期 miR-15a-5p 显著升高（p=0.0002）。
PD-1 和 TIM3 在耗尽的 T 淋巴细胞中的表达模式不仅在正常妊娠和 RPL 妇女之间不同，而且在妊娠的不同阶段也不同。因此，我们的结果表明这些标志物在不同妊娠阶段调节淋巴细胞活性中的作用。
