Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center, USA.
Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center, USA.
Placenta. 2018 Sep;69:1-8. doi: 10.1016/j.placenta.2018.07.006. Epub 2018 Jul 10.
Cytokines modulate fetal well-being and contribute to parturition. Their origin in fetal blood, whether maternal, placental or fetal, at the time of parturition remains unclear.
To determine fetal and placental contributions to circulating fetal cytokines by measuring umbilical arterial (UmA) and venous (UmV) concentration differences in uncomplicated term pregnancies in the absence and presence of labor.
Term uncomplicated pregnancies were assessed: Group 1 were not in labor and delivered by elective cesarean section (n = 20); Group 2 delivered vaginally following uncomplicated pregnancy and labor (n = 30). UmA and UmV blood was collected before delivery of the placenta to measure circulating cytokines. Placental tissue was collected for histology and to determine cytokine contents and localization.
Group 1 UmA and UmV IL-10 concentrations were similar (504 ± 15 and 468 ± 16 pg/ml, respectively; P ≥ 0.1); other cytokines were below level of detection. During labor, IL-10 concentrations increased 15-34%, but placental contents decreased. Group 2 UmA IL-6 and IL-8 concentrations increased (P < 0.001) to 16.7 ± 1.6 and 18.4 ± 4.3 pg/ml, respectively, but were less (P < 0.001) in UmV, 0.29 ± 0.2 and 0.74 ± 0.3 pg/ml, respectively, demonstrating placental clearances ≥97%. This was associated with >6-fold increases in placental IL-6/IL-8 contents (P < 0.001) and chorioamniotic infiltration of activated maternal neutrophils. IL-6 and IL-10 were localized to villous syncytiotrophoblasts.
In uncomplicated term pregnancies fetal circulating IL-10 is likely of placental origin, whereas IL-6/IL-8 are derived from the fetus, increase during parturition, and circulating levels are modulated by non-saturable placental clearance, revealing a novel pathway for fetal-placental crosstalk and signaling.
细胞因子调节胎儿健康，并有助于分娩。在分娩时，其在胎儿血液中的来源（母体、胎盘或胎儿）尚不清楚。
通过测量无分娩和分娩时的正常足月妊娠的脐动脉（UmA）和脐静脉（UmV）浓度差，确定胎儿和胎盘对循环胎儿细胞因子的贡献。
评估正常足月妊娠：第 1 组未分娩，择期行剖宫产术（n=20）；第 2 组正常分娩（n=30）。分娩前采集脐动脉和脐静脉血样，以测量循环细胞因子。采集胎盘组织进行组织学检查，并确定细胞因子含量和定位。
第 1 组的 UmA 和 UmV 白细胞介素 10（IL-10）浓度相似（分别为 504±15 和 468±16 pg/ml；P≥0.1）；其他细胞因子低于检测水平。在分娩过程中，IL-10 浓度增加 15-34%，但胎盘含量下降。第 2 组的 UmA 白细胞介素 6（IL-6）和白细胞介素 8（IL-8）浓度升高（P<0.001），分别为 16.7±1.6 和 18.4±4.3 pg/ml，但在 UmV 中浓度较低（P<0.001），分别为 0.29±0.2 和 0.74±0.3 pg/ml，表明胎盘清除率≥97%。这与胎盘 IL-6/IL-8 含量增加>6 倍（P<0.001）和激活的母体中性粒细胞向绒毛膜羊膜炎的浸润有关。IL-6 和 IL-10 定位于绒毛合胞体滋养层。
在正常足月妊娠中，胎儿循环中的白细胞介素 10 可能来源于胎盘，而白细胞介素 6/8 则来源于胎儿，在分娩过程中增加，循环水平受非饱和胎盘清除率调节，揭示了胎儿-胎盘相互作用和信号传递的新途径。
