Pregnancy Health and Beyond Laboratory, Flinders Health and Medical Research Institute, Flinders University, Adelaide, SA, Australia.
South Australian Genomics Centre, South Australian Health & Medical Research Institute, Adelaide, SA, Australia.
Front Immunol. 2022 Mar 25;13:807750. doi: 10.3389/fimmu.2022.807750. eCollection 2022.
Parturition signals the end of immune tolerance in pregnancy. Term labour is usually a sterile inflammatory process triggered by damage associated molecular patterns (DAMPs) as a consequence of functional progesterone withdrawal. Activation of DAMPs recruits leukocytes and inflammatory cytokine responses in the myometrium, decidua, cervix and fetal membranes. Emerging evidence shows components of the inflammasome are detectable in both maternal decidua and placenta. However, the activation of the placental inflammasome with respect to mode of delivery has not been profiled. Placental chorionic villus samples from women delivering at term unassisted vaginal (UV) birth, labouring lower segment caesarean section (LLSCS, emergency caesarean section) and prelabour lower segment caesarean section (PLSCS, elective caesarean section) underwent high throughput RNA sequencing (NextSeq Illumina) and bioinformatic analyses to identify differentially expressed inflammatory (DE) genes. DE genes (, , , , , , , and ), as well as common inflammasome genes (, , , , , , , , and ), were targets for further qPCR analyses and Western blotting to quantify protein expression. There was no specific sensor molecule-activated inflammasome which dominated expression when stratified by mode of delivery, implying that multiple inflammasomes may function synergistically during parturition. Whilst placentae from women who had UV births overall expressed pro-inflammatory mediators, placentae from LLSCS births demonstrated a much greater pro-inflammatory response, with additional interplay of pro- and anti-inflammatory mediators. As expected, inflammasome activation was very low in placentae from women who had PLSCS births. Sex-specific differences were also detected. Placentae from male-bearing pregnancies displayed higher inflammasome activation in LLSCS compared with PLSCS, and placentae from female-bearing pregnancies displayed higher inflammasome activation in LLSCS compared with UV. In conclusion, placental inflammasome activation differs with respect to mode of delivery and neonatal sex. Its assessment may identify babies who have been exposed to aberrant inflammation at birth that may compromise their development and long-term health and wellbeing.
分娩标志着妊娠免疫耐受的结束。足月分娩通常是一种无菌性炎症过程，由功能孕酮撤退引起的损伤相关分子模式（DAMPs）触发。DAMPs 的激活招募白细胞和肌层、蜕膜、宫颈和胎膜中的炎症细胞因子反应。新出现的证据表明，母体蜕膜和胎盘中都可检测到炎症小体的成分。然而，分娩方式对胎盘炎症小体的激活尚未得到描述。来自足月阴道自然分娩（UV）、下段剖宫产（LLSCS，紧急剖宫产）和术前下段剖宫产（PLSCS，择期剖宫产）产妇的胎盘绒毛膜绒毛样本进行高通量 RNA 测序（NextSeq Illumina）和生物信息学分析，以鉴定差异表达的炎症（DE）基因。DE 基因（、、、、、、、和）以及常见的炎症小体基因（、、、、、、、和）是进一步 qPCR 分析和 Western blot 分析以量化蛋白表达的目标。根据分娩方式分层时，没有特定的传感器分子激活的炎症小体占主导地位，这意味着在分娩过程中可能有多个炎症小体协同作用。虽然来自 UV 分娩的产妇胎盘总体上表达促炎介质，但来自 LLSCS 分娩的胎盘表现出更强的促炎反应，同时存在促炎和抗炎介质的相互作用。如预期的那样，来自 PLSCS 分娩的产妇胎盘中的炎症小体激活非常低。还检测到性别特异性差异。与 PLSCS 相比，来自男性胎儿妊娠的胎盘在 LLSCS 中显示出更高的炎症小体激活，而来自女性胎儿妊娠的胎盘在 LLSCS 中显示出比 UV 更高的炎症小体激活。总之，胎盘炎症小体的激活与分娩方式和新生儿性别有关。对其进行评估可能可以识别在出生时暴露于异常炎症的婴儿，这可能会影响他们的发育以及长期健康和幸福感。
