Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study
Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study
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DOI：
10.1152/ajpregu.00324.2019
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发表时间：
2020-02-01
影响因子：
2.8
通讯作者：
Goulopoulou, Styliani
中科院分区：
文献类型：
--
作者：
Cushen, Spencer C.;Sprouse, Marc L.;Goulopoulou, Styliani
由于细胞死亡而暴露于细胞外空间的线粒体DNA（mtDNA）具有免疫刺激特性。病例对照研究报告了先兆子痫发生几率与循环mtDNA之间的正相关性。这些发现是基于相对定量方案，不允许确定的mtDNA的绝对浓度，是高度敏感的核DNA污染。此外，循环mtDNA浓度响应正常妊娠，这是一种炎症状态，其特征是连续的胎盘细胞凋亡，尚未建立。本研究的主要目的是确定健康孕妇从孕前到孕早期、孕晚期和产后循环mtDNA的纵向变化。使用TaqMan探针和化学对来自血清的全基因组提取物进行mtDNA和核DNA（nDNA）的绝对实时PCR定量。血清游离mtDNA和nDNA浓度在孕晚期高于孕早期和产后。在出生身长分布的上四分位数怀上新生儿的孕妇在妊娠晚期的mtDNA浓度高于在出生身长分布的下四分位数怀上新生儿的孕妇。循环mtDNA和nDNA浓度之间的相关性因性别而异（即，怀孕携带女性与男性胎儿）。这项研究是第一个建立时间模式的循环无细胞mtDNA浓度在正常人妊娠使用绝对DNA定量技术。在正常妊娠中循环mtDNA的浓度可用作临床预后或诊断测试的发展，在孕妇或在发展中国家，妊娠并发症的风险的参考值。
Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.