Fjeldstad Heidi E, Jacobsen Daniel P, Johnsen Guro M, Sugulle Meryam, Chae Angel, Kanaan Sami B, Gammill Hilary S, Staff Anne Cathrine
Faculty of Medicine, University of Oslo, Norway; Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway.
Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway.
J Reprod Immunol. 2024 Mar;162:104206. doi: 10.1016/j.jri.2024.104206. Epub 2024 Jan 20.
Fetal microchimerism (FMc) arises when fetal cells enter maternal circulation, potentially persisting for decades. Increased FMc is associated with fetal growth restriction, preeclampsia, and anti-angiogenic shift in placenta-associated proteins in diabetic and normotensive term pregnancies. The two-stage model of preeclampsia postulates that placental dysfunction causes such shift in placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLt-1), triggering maternal vascular inflammation and endothelial dysfunction. We investigated whether anti-angiogenic shift, fetal sex, fetal growth restriction, and severe maternal hypertension correlate with FMc in hypertensive disorders of pregnancy with new-onset features (n = 125). Maternal blood was drawn pre-delivery at > 25 weeks' gestation. FMc was detected by quantitative polymerase chain reaction targeting paternally inherited unique fetal alleles. PlGF and sFlt-1 were measured by immunoassay. We estimated odds ratios (ORs) by logistic regression and detection rate ratios (DRRs) by negative binomial regression. PlGF correlated negatively with FMc quantity (DRR = 0.2, p = 0.005) and female fetal sex correlated positively with FMc prevalence (OR = 5.0, p < 0.001) and quantity (DRR = 4.5, p < 0.001). Fetal growth restriction no longer correlated with increased FMc quantity after adjustment for correlates of placental dysfunction (DRR = 1.5, p = 0.272), whereas severe hypertension remained correlated with both FMc measures (OR = 5.5, p = 0.006; DRR = 6.3, p = 0.001). Our findings suggest that increased FMc is independently associated with both stages of the two-stage preeclampsia model. The association with female fetal sex has implications for microchimerism detection methodology. Future studies should target both male and female-origin FMc and focus on clarifying which placental mechanisms impact fetal cell transfer and how FMc impacts the maternal vasculature.
当胎儿细胞进入母体循环时会出现胎儿微嵌合体（FMc），其可能会持续数十年。FMc增加与胎儿生长受限、先兆子痫以及糖尿病和血压正常的足月妊娠中胎盘相关蛋白的抗血管生成转变有关。先兆子痫的两阶段模型假定胎盘功能障碍会导致胎盘生长因子（PlGF）和可溶性fms样酪氨酸激酶-1（sFLt-1）发生这种转变，从而引发母体血管炎症和内皮功能障碍。我们调查了抗血管生成转变、胎儿性别、胎儿生长受限和严重母体高血压是否与具有新发特征的妊娠高血压疾病中的FMc相关（n = 125）。在妊娠>25周时分娩前采集母体血液。通过靶向父系遗传的独特胎儿等位基因的定量聚合酶链反应检测FMc。通过免疫测定法测量PlGF和sFlt-1。我们通过逻辑回归估计比值比（OR），通过负二项回归估计检测率比（DRR）。PlGF与FMc数量呈负相关（DRR = 0.2，p = 0.005），女性胎儿性别与FMc患病率呈正相关（OR = 5.0，p < 0.001）和数量（DRR = 4.5，p < 0.001）。在调整胎盘功能障碍的相关因素后，胎儿生长受限与FMc数量增加不再相关（DRR = 1.5，p = 0.272），而严重高血压与两种FMc测量指标均相关（OR = 5.5，p = 0.006；DRR = 6.3，p = 0.001）。我们的研究结果表明，FMc增加与先兆子痫两阶段模型的两个阶段均独立相关。与女性胎儿性别的关联对微嵌合体检测方法有影响。未来的研究应针对男性和女性来源的FMc，并专注于阐明哪些胎盘机制影响胎儿细胞转移以及FMc如何影响母体血管系统。
