Objectives It is not clear, which factors affect extracellular DNA (ecDNA) concentrations in healthy women with singleton uncomplicated pregnancies, although deoxyribonucleases (DNases) are hypothesized to be responsible for the cleavage of plasma ecDNA. The aim of this study was to analyze potential determinants of total ecDNA including plasma DNase activity. Methods Plasma samples were collected from 48 healthy women with singleton uncomplicated pregnancies in the third trimester (gestation week 37). DNA was isolated and quantified using fluorometry and real time PCR. DNase activity was assessed using the single radial enzyme-diffusion method. Results Neither ecDNA, nor DNase activity were affected by maternal age or BMI. DNase activity negatively correlated with total plasma ecDNA (r=−0.40, p=0.007). Similar associations were found for ecDNA of nuclear and mitochondrial origin, but not with fetal DNA quantified using Y-targeted PCR in male fetus-bearing pregnancies. Conclusions The role of plasma ecDNA of fetal and maternal origin is studied in the pathogenesis of pregnancy-complications. The results indicate that plasma DNase activity could negatively regulate ecDNA concentrations and should, thus, be analyzed in preeclampsia, preterm birth and other ecDNA-related pregnancy complications.

中文翻译：

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妊娠晚期无并发症的单胎妊娠中脱氧核糖核酸酶活性与细胞外 DNA 呈负相关


目的 目前尚不清楚哪些因素会影响无并发症的单胎健康女性的细胞外 DNA (ecDNA) 浓度，但假设脱氧核糖核酸酶 (DNase) 负责血浆 ecDNA 的切割。本研究的目的是分析总 ecDNA 的潜在决定因素，包括血浆 DNase 活性。方法 采集 48 名孕晚期（妊娠第 37 周）无并发症单胎妊娠的健康女性的血浆样本。使用荧光测定法和实时 PCR 分离并定量 DNA。使用单径向酶扩散法评估 DNA 酶活性。结果 ecDNA 和 DNase 活性均不受母亲年龄或 BMI 的影响。 DNase 活性与总血浆 ecDNA 呈负相关（r=-0.40，p=0.007）。核和线粒体来源的 ecDNA 也发现了类似的关联，但与男性胎儿妊娠中使用 Y 靶向 PCR 定量的胎儿 DNA 没有发现类似的关联。结论 研究了胎儿和母体血浆 ecDNA 在妊娠并发症发病机制中的作用。结果表明，血浆 DNase 活性可以负向调节 ecDNA 浓度，因此应在先兆子痫、早产和其他与 ecDNA 相关的妊娠并发症中进行分析。