Golden Thea N, Mani Sneha, Linn Rebecca L, Leite Rita, Trigg Natalie A, Wilson Annette, Anton Lauren, Mainigi Monica, Conine Colin C, Kaufman Brett A, Strauss Jerome F, Parry Samuel, Simmons Rebecca A
Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Center for Women's Health and Reproductive Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Extracell Vesicles. 2025 Apr;14(4):e70051. doi: 10.1002/jev2.70051.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) cause placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro. Trophoblast exposure to EVs isolated from patients with an active infection (AI), but not controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an AI, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19, depending on the gestational timing of infection, and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs, and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染及由此导致的冠状病毒病（COVID-19）会引起胎盘功能障碍，从而增加不良妊娠结局的风险。虽然COVID-19导致的胎盘病理异常很常见，但胎盘的直接感染却很罕见。这表明，与母体COVID-19相关的病理生理学，而非胎盘直接感染，是胎盘功能障碍的原因。我们推测，孕期因COVID-19而改变的母体循环细胞外囊泡（EVs）会导致胎盘功能障碍。为验证这一假设，我们对COVID-19合并妊娠的循环EVs进行了表征，并在体外测试了它们对滋养层细胞生理学的影响。将滋养层细胞暴露于从活跃感染（AI）患者而非对照组分离出的EVs中，会改变关键的滋养层细胞功能，包括激素分泌和侵袭。因此，来自有症状和无症状AI参与者的循环EVs会破坏重要的滋养层细胞功能。COVID-19参与者与对照组之间的EV货物存在差异，这可能取决于感染的孕周，这种差异可能会导致胎盘转录组和形态的破坏。我们的研究结果表明，COVID-19在整个孕期都会对循环EVs产生影响，且循环EVs很可能参与了COVID-19诱导的胎盘功能障碍。
