Department of Clinical Sciences, Section of Woman Health Science, Università Politecnica Marche, Ancona, Italy.
Cytokine. 2012 Apr;58(1):50-6. doi: 10.1016/j.cyto.2011.12.019. Epub 2012 Jan 21.
To investigate the inflammatory cytokine expression pattern in trophoblastic tissue from women with unexplained recurrent miscarriage (RM).
Trophoblasts were obtained during uterine evacuation from 11 women with RM and from 20 healthy pregnant women undergoing elective termination of pregnancy, who served as controls. The array was performed using GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015 membranes. Data were confirmed by quantitative real-time PCR. The Mann-Whitney U test was performed for statistical analysis.
Microarray analysis identified three genes that were differentially expressed between RM patients and controls. We observed significant downregulation of Transforming Growth Factor beta 3 (TGF-β3) and Interleukin 25 (IL-25) (5-fold reduction and 2.5-fold reduction, respectively) and significant upregulation of CD-25, also known as Interleukin 2 receptor alpha (IL-2RA) (7-fold increase) in women with RM compared with controls. The median ΔC(t) of TGF-β3 was 8.2 (interquartile range, 7.67-8.9) in RM patients vs. 5.85 (interquartile range, 5.3-6.09) in controls; the median ΔC(t) of IL-25 was 5.18 (interquartile range, 4.46-5.76) in RM patients vs. 3.85 (interquartile range, 3.6-4.51) in controls, and the median ΔC(t) of CD-25 was 9.62 (interquartile range, 7.81-12.42) in RM patients vs. 12.44 (interquartile range, 11.02-13.86) in controls.
Our results suggest that the immunological and inflammatory regulation mechanisms of the placental environment play a key role in recurrent miscarriage. The observed trophoblast cytokine expression pattern at the maternal-fetal interface confirms the immunotrophic theory, as demonstrated by a switch from a T-helper-1 (Th1) profile to a T-helper-2 (Th2) profile in women who experience recurrent miscarriages.
探讨原因不明复发性流产（RM）患者胎盘组织中炎症细胞因子的表达模式。
在 11 例 RM 患者和 20 例因选择性终止妊娠而行子宫排空术的健康孕妇中获取绒毛组织，后者作为对照。采用 GEArray Q 系列人类炎症细胞因子和受体基因阵列 HS-015 膜进行阵列分析。通过定量实时 PCR 对数据进行确认。采用 Mann-Whitney U 检验进行统计学分析。
微阵列分析鉴定出在 RM 患者和对照组之间差异表达的 3 个基因。我们观察到，与对照组相比，RM 患者中转化生长因子β 3（TGF-β3）和白细胞介素 25（IL-25）显著下调（分别下调 5 倍和 2.5 倍），白细胞介素 2 受体α（IL-2RA）即 CD-25 显著上调（上调 7 倍）。RM 患者的 TGF-β3 中位 ΔC(t)为 8.2（四分位距，7.67-8.9），而对照组为 5.85（四分位距，5.3-6.09）；IL-25 的中位 ΔC(t)在 RM 患者中为 5.18（四分位距，4.46-5.76），而对照组为 3.85（四分位距，3.6-4.51），CD-25 的中位 ΔC(t)在 RM 患者中为 9.62（四分位距，7.81-12.42），而对照组为 12.44（四分位距，11.02-13.86）。
我们的结果表明，胎盘环境的免疫和炎症调节机制在复发性流产中起着关键作用。在母体-胎儿界面观察到的滋养细胞细胞因子表达模式证实了免疫营养理论，这是通过在经历复发性流产的女性中从 Th1 向 Th2 模式的转变来证明的。
