Sarr Demba, Andrew Alicer K, Shukla Ashish K, Mwalimu Stephen, Moore Julie M
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Center for Tropical and Emering Global Diseases, University of Georgia, Athens, Georgia, USA.
J Infect Dis. 2025 Jul 30;232(1):e174-e185. doi: 10.1093/infdis/jiaf243.
Placental malaria is characterized by the accumulation of Plasmodium falciparum-infected erythrocytes and maternal inflammation in the intervillous spaces of the placenta. These features are associated with placental damage and fetal compromise. However, understanding of the mechanisms that lead to poor pregnancy outcome and interventions targeting excessive host responses to placental malaria are still lacking. The syncytiotrophoblast, a cell of fetal origin, is known to be responsive to malaria-infected erythrocytes as well as the malaria toxin, hemozoin, but its susceptibility to oxidative stress and how this might contribute to placental damage and dysfunction has not yet been directly investigated.
The characteristics and key drivers of the syncytiotrophoblast response to oxidative stress were investigated using ex vivo human placental tissues and primary trophoblasts isolated from healthy pregnant women. Primary syncytiotrophoblast was exposed to hemozoin and tumor necrosis factor, a critical inflammatory cytokine, to model conditions found in human placental malaria.
The data show remarkable lipid peroxidation in human placental samples from a malaria endemic setting and evidence of a modulated antioxidant response at the transcriptional level. Likewise, primary human syncytiotrophoblast exposed to hemozoin, tumor necrosis factor, and tumor necrosis factor combined with hemozoin in vitro exhibited increased markers of an antioxidative response, and, with hemozoin alone, oxidation of lipids and DNA.
These results suggest that oxidative stress in syncytiotrophoblast is promoted by both hemozoin exposure and maternal inflammatory responses to placental malaria, and contribute to an increased understanding of placental dysfunction and compromise in this infection.
胎盘疟疾的特征是恶性疟原虫感染的红细胞在胎盘绒毛间隙积聚以及母体炎症。这些特征与胎盘损伤和胎儿窘迫有关。然而，对于导致不良妊娠结局的机制以及针对宿主对胎盘疟疾过度反应的干预措施仍缺乏了解。合体滋养层细胞是一种胎儿来源的细胞，已知对疟疾感染的红细胞以及疟疾毒素疟色素有反应，但其对氧化应激的敏感性以及这可能如何导致胎盘损伤和功能障碍尚未得到直接研究。
使用来自健康孕妇的离体人胎盘组织和原代滋养层细胞研究合体滋养层细胞对氧化应激反应的特征和关键驱动因素。将原代合体滋养层细胞暴露于疟色素和肿瘤坏死因子（一种关键的炎性细胞因子），以模拟人胎盘疟疾中的情况。
数据显示，来自疟疾流行地区的人胎盘样本中存在明显的脂质过氧化，并且在转录水平上有调节抗氧化反应的证据。同样，体外暴露于疟色素、肿瘤坏死因子以及肿瘤坏死因子与疟色素组合的原代人合体滋养层细胞表现出抗氧化反应标志物增加，并且仅暴露于疟色素时会出现脂质和DNA氧化。
这些结果表明，疟色素暴露和母体对胎盘疟疾的炎症反应均会促进合体滋养层细胞中的氧化应激，并有助于加深对这种感染中胎盘功能障碍和损害的理解。
