Michigan State University Department of Microbiology and Molecular Genetics, East Lansing, MI, United States; Michigan State University Institute for Quantitative Health Science and Engineering, East Lansing, MI, United States.
Stanford University School of Medicine Molecular Imaging Program, Department of Radiology, Stanford, CA, United States; Stanford University School of Medicine Division of Gastroenterology and Hepatology, Department of Medicine, Stanford, CA, United States.
Placenta. 2022 Oct;128:29-35. doi: 10.1016/j.placenta.2022.08.001. Epub 2022 Aug 23.
Placental infection and inflammation are risk factors for adverse pregnancy outcomes, including preterm labor. However, the mechanisms underlying these outcomes are poorly understood.
To study this response, we have employed a pregnant mouse model of placental infection caused by the bacterial pathogen Listeria monocyogenes, which infects the human placenta. Through in vivo bioluminescence imaging, we confirm the presence of placental infection and quantify relative infection levels. Infected and control placentas were collected on embryonic day 18 for RNA sequencing to evaluate gene expression signatures associated with infection by Listeria.
We identified an enrichment of genes associated with eicosanoid biosynthesis, suggesting an increase in eicosanoid production in infected tissues. Because of the known importance of eicosanoids in inflammation and timing of labor, we quantified eicosanoid levels in infected and uninfected placentas using semi-targeted mass spectrometry. We found a significant increase in the concentrations of several key eicosanoids: leukotriene B4, lipoxin A4, prostaglandin A2, prostaglandin D2, and eicosatrienoic acid.
Our study provides a likely explanation for dysregulation of the timing of labor following placental infection. Further, our results suggest potential biomarkers of placental pathology and targets for clinical intervention.
胎盘感染和炎症是不良妊娠结局的风险因素，包括早产。然而，这些结果的机制尚不清楚。
为了研究这种反应，我们采用了一种由细菌病原体李斯特菌引起的胎盘感染的妊娠小鼠模型，该病原体感染人类胎盘。通过体内生物发光成像，我们确认存在胎盘感染并量化相对感染水平。在胚胎第 18 天收集感染和对照胎盘进行 RNA 测序，以评估与李斯特菌感染相关的基因表达特征。
我们发现与类二十烷酸生物合成相关的基因富集，表明感染组织中类二十烷酸的产生增加。由于类二十烷酸在炎症和分娩时间中的已知重要性，我们使用半靶向质谱法定量了感染和未感染胎盘中的类二十烷酸水平。我们发现几种关键类二十烷酸的浓度显著增加：白三烯 B4、脂氧素 A4、前列腺素 A2、前列腺素 D2 和二十碳三烯酸。
我们的研究为胎盘感染后分娩时间失调提供了一个可能的解释。此外，我们的结果表明了胎盘病理学的潜在生物标志物和临床干预的目标。
