Wu Guangping, Li Rong, Tong Chao, He Miaonan, Qi Zhiwei, Chen Huijuan, Deng Tao, Liu Hailiang, Qi Hongbo
1Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 People's Republic of China.
2State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016 People's Republic of China.
Mol Cytogenet. 2019 Aug 30;12:38. doi: 10.1186/s13039-019-0451-3. eCollection 2019.
Pregnancy complications could lead to maternal and fetal morbidity and mortality. Early diagnosing and managing complications have been associated with good outcomes. The placenta was an important organ for development of pregnancy complications. Thus, non-invasive prenatal testing technologies could detect genetic variations, such as aneuploidies and sub-chromosomal copy number variations, reflecting defective placenta by maternal plasma cffDNAs. Maternal cffDNAs had been proved to derive from trophoblast cells of placenta.
In order to find out the relationship between genetic variations and pregnancy complications, we reviewed NIPT results for subchromosomal copy number variations in a cohort of 3890 pregnancies without complications and 441 pregnancies with pregnancy complications including gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preterm prelabor rupture of membranes (PPROM) and placenta implantation abnormalities (PIA). For GDMs, we identified three CNV regions containing some members of alpha- and beta-defensins, such as DEFA1, DEFA3, DEFB1. For PIHs, we found three duplication and one deletion region including Pcdhα, Pcdhβ, and Pcdhγ, known as protocadherins, which were complicated by hypertensive disorders. For PPROMs and PIAs, we identified one and two CNV regions, respectively. SFTPA2, SFTPD and SFTPA1, belonging to surfactant protein, was considered to moderated the inflammatory activation within the fetal extra-embryonic compartment, associated to duration of preterm prelabor rupture of fetal membranes, while MEF2C and TM6SF1 could be involved in trophoblast invasion and differentiation.
Our findings gave a clue to correlation between genetic variations of maternal cell-free DNAs and pregnancy complications.
妊娠并发症可导致母婴发病和死亡。早期诊断和处理并发症与良好结局相关。胎盘是妊娠并发症发生发展的重要器官。因此，无创产前检测技术可检测遗传变异，如非整倍体和亚染色体拷贝数变异，通过母体血浆中胎儿游离DNA反映胎盘缺陷。已证实母体胎儿游离DNA来源于胎盘滋养层细胞。
为了找出遗传变异与妊娠并发症之间的关系，我们回顾了3890例无并发症妊娠和441例有妊娠并发症（包括妊娠期糖尿病（GDM）、妊娠高血压（PIH）、胎膜早破（PPROM）和胎盘植入异常（PIA））的亚染色体拷贝数变异的无创产前检测结果。对于妊娠期糖尿病，我们确定了三个拷贝数变异区域，其中包含一些α-和β-防御素成员，如DEFA1、DEFA3、DEFB1。对于妊娠高血压，我们发现了三个重复区域和一个缺失区域，包括原钙黏蛋白Pcdhα、Pcdhβ和Pcdhγ，这些区域与高血压疾病相关。对于胎膜早破和胎盘植入异常，我们分别确定了一个和两个拷贝数变异区域。属于表面活性蛋白的SFTPA2、SFTPD和SFTPA1被认为可调节胎儿胚外腔室内的炎症激活，这与胎膜早破的持续时间有关，而MEF2C和TM6SF1可能参与滋养层细胞的侵袭和分化。
我们的研究结果为母体游离DNA的遗传变异与妊娠并发症之间的相关性提供了线索。
