Departments of Pediatrics David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Epigenetics. 2021 Jun;16(6):642-661. doi: 10.1080/15592294.2020.1816774. Epub 2020 Oct 13.
Although analysis of maternal plasma cell-free content has been employed for screening of genetic abnormalities within a pregnancy, limited attention has been paid to its use for the detection of adverse pregnancy outcomes (APOs) based on placental function. Here we investigated cell-free DNA and RNA content of 102 maternal and 25 cord plasma samples. Employing a novel deconvolution methodology, we found that during the first trimester, placenta-specific DNA increased prior to the subsequent development of gestational diabetes with no change in patients with preeclampsia while decreasing with maternal obesity. Moreover, using cell-free RNA sequencing, APOs revealed 71 differentially expressed genes early in pregnancy. We noticed the upregulation of S100A8, MS4A3, and MMP8 that have been already associated with APOs but also the upregulation of BCL2L15 and the downregulation of ALPL that have never been associated with APOs. We constructed a classifier with a positive predictive ability (AUC) of 0.91 for APOs, 0.86 for preeclampsia alone and 0.64 for GDM. We conclude that placenta-specific cell-free nucleic acids during early gestation provide the possibility of predicting APOs prior to the emergence of characteristic clinical features.
虽然已经将母体血浆无细胞内容物的分析用于筛查妊娠中的遗传异常，但基于胎盘功能，对其用于检测不良妊娠结局（APO）的关注有限。在这里，我们研究了 102 份母体和 25 份脐带血浆样本的无细胞 DNA 和 RNA 含量。采用一种新的解卷积方法，我们发现，在妊娠早期，胎盘特异性 DNA 增加，随后发生妊娠期糖尿病，而先兆子痫患者没有变化，而随着母体肥胖，胎盘特异性 DNA 减少。此外，使用无细胞 RNA 测序，在妊娠早期发现了 71 个差异表达的基因。我们注意到与 APO 相关的 S100A8、MS4A3 和 MMP8 的上调，但也注意到 BCL2L15 的上调和 ALPL 的下调，这些基因从未与 APO 相关。我们构建了一个分类器，其对 APO 的阳性预测能力（AUC）为 0.91，对单独的子痫前期为 0.86，对 GDM 为 0.64。我们得出结论，妊娠早期胎盘特异性无细胞核酸为预测出现特征性临床特征之前的 APO 提供了可能。
