Baev O R, Karapetian A O, Nizyaeva N V, Sadekova А А, Krasniy A M
V. I. Kulakov National Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russian Federation, Moscow, Russia.
Department of Obstetrics, Gynecology, Perinatology, and Reproductology, I. M. Sechenov First Moscow State Medical University, Ministry of Health of Russian Federation (Sechenov University), Moscow, Russia.
Bull Exp Biol Med. 2019 Nov;168(1):145-149. doi: 10.1007/s10517-019-04665-z. Epub 2019 Nov 25.
We evaluated the content of cell-free fetal DNA in maternal blood and expression of ZBP-1 receptors in the placental tissue of women with uncomplicated pregnancy, preeclampsia, and preterm labor. The study included 16 women with preeclampsia (early and late-onset preeclampsia, 8 cases each), 16 women with preterm labor, and 21 women with uncomplicated pregnancy. The concentration of cell-free fetal DNA was measured by PCR by detecting hypermethylated region of the RASSF1A gene. Immunohistochemistry was performed on paraffin-embedded sections of the placenta samples using primary polyclonal antibodies to ZBP-1. Significant increase in the level of cell-free fetal DNA was found in women with preeclampsia (both early and late-onset form) in comparison with uncomplicated pregnancy. The concentration of cell-free fetal DNA in preterm labor group did not differ from the control group; however, it was significantly lower than in early-onset preeclampsia, but not late preeclampsia. Immunohistochemical study showed higher expression of ZBP-1 in the villus syncytiotrophoblast in early-onset preeclampsia in comparison with that in preterm labor group (p=0.006). Fragments of damaged placental cells, predominantly trophoblast, enter maternal circulation and are the source of cell-free fetal DNA and a potential ligand for ZBP-1, which leads to further cell damage and the formation of a vicious circle. The increase in the content of cell-free fetal DNA in maternal blood and ZBP-1 expression in the syncytiotrophoblast in preeclampsia are interrelated processes reflecting impaired morphofunctional state of the placenta.
我们评估了正常妊娠、子痫前期和早产孕妇母血中游离胎儿DNA的含量以及胎盘组织中ZBP-1受体的表达。该研究纳入了16名单纯子痫前期患者(早发型和晚发型子痫前期各8例)、16名早产孕妇以及21名正常妊娠孕妇。通过检测RASSF1A基因的高甲基化区域,采用聚合酶链反应(PCR)测定游离胎儿DNA的浓度。使用抗ZBP-1的多克隆一抗对胎盘样本的石蜡包埋切片进行免疫组织化学检测。与正常妊娠孕妇相比,子痫前期患者(早发型和晚发型)母血中游离胎儿DNA水平显著升高。早产组游离胎儿DNA浓度与对照组无差异;然而,其显著低于早发型子痫前期组,但与晚发型子痫前期组无差异。免疫组织化学研究显示,早发型子痫前期绒毛合体滋养层中ZBP-1的表达高于早产组(p = 0.006)。受损胎盘细胞的碎片,主要是滋养层细胞,进入母体循环,是游离胎儿DNA的来源以及ZBP-1的潜在配体,这会导致进一步的细胞损伤并形成恶性循环。子痫前期孕妇母血中游离胎儿DNA含量的增加以及合体滋养层中ZBP-1表达的增加是相互关联的过程,反映了胎盘形态功能状态受损。