Nobrega Guilherme M, McColl Eliza R, Antolini-Tavares Arthur, Souza Renato T, Cecatti José Guilherme, Costa Maria Laura, Mysorekar Indira U
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA.
Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
Am J Reprod Immunol. 2025 Jan;93(1):e70034. doi: 10.1111/aji.70034.
COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.
In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 term, 4 preterm) compared to uninfected controls (n = 10 term, 3 preterm). The placentas were analyzed for SARS-CoV-2 infection (spike and nucleocapsid viral proteins), markers of DNA damage (γH2AX) and oxidative stress (ROS), and senescence (telomere length, cell cycle regulators, and senescence-associated secretory phenotype [SASP]).
Although no overall differences in cellular senescence markers were observed between the COVID-19 positive and negative groups, we found increased secreted SASP markers. Confocal microscopy of placentas from COVID-19 positive cases revealed localized areas of oxidative stress and DNA damage colocalized with SARS-CoV-2 spike protein.
These findings indicate that SARS-CoV-2 infection induces localized focal placental damage, warranting further investigation into its impact on maternal and perinatal outcomes.
孕期感染新型冠状病毒肺炎（COVID-19）与孕产妇发病率增加和早产（PTB）发生率较高有关，但其潜在机制仍不清楚。细胞衰老以细胞分裂的不可逆停止为特征，是胎盘功能中的一个关键过程，其失调与PTB等妊娠并发症有关。衰老可由多种应激源诱导，包括氧化应激、DNA损伤和病毒感染。
在本研究中，我们确定了COVID-19是否对胎盘衰老有影响。我们检查了感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的女性的胎盘（足月产10例，早产4例），并与未感染的对照组（足月产10例，早产3例）进行比较。分析胎盘的SARS-CoV-2感染情况（刺突蛋白和核衣壳病毒蛋白）、DNA损伤标志物（γH2AX）和氧化应激标志物（ROS）以及衰老情况（端粒长度、细胞周期调节因子和衰老相关分泌表型[SASP]）。
尽管在COVID-19阳性和阴性组之间未观察到细胞衰老标志物的总体差异，但我们发现分泌的SASP标志物增加。对COVID-19阳性病例胎盘的共聚焦显微镜检查显示，氧化应激和DNA损伤的局部区域与SARS-CoV-2刺突蛋白共定位。
这些发现表明，SARS-CoV-2感染会引起局部胎盘损伤，有必要进一步研究其对孕产妇和围产期结局的影响。
