Kramer Anita W, Lamale-Smith Leah M, Winn Virginia D
University of Colorado School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Aurora, CO, USA.
Placenta. 2016 Jan;37:19-25. doi: 10.1016/j.placenta.2015.11.004. Epub 2015 Nov 23.
Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia.
Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera.
PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood.
PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation.
妊娠相关血浆蛋白A2（PAPP-A2）是一种与妊娠相关的胰岛素样生长因子结合蛋白5（IGFBP-5）蛋白酶，已知在子痫前期水平会升高。由于胰岛素样生长因子在人类着床和胎盘形成过程中起着重要作用，我们试图确定PAPP-A2在正常妊娠和子痫前期妊娠整个孕期的表达模式，以评估其在胎盘发育和子痫前期发病机制中的作用。
从子痫前期和对照妊娠中获取胎盘基底板和绒毛样本、母血和胎儿脐血血清。对整个孕期的福尔马林固定组织切片进行细胞角蛋白-7、HLA-G和PAPP-A2染色。还对蛋白裂解物和血清进行了PAPP-A2免疫印迹分析。
PAPP-A2主要由分化的滋养层细胞和胎儿内皮细胞表达。绒毛膜绒毛在孕早期表达强烈，随后在孕中期逐渐下降，在孕晚期又恢复。PAPP-A2的表达不受分娩影响。与对照组相比，子痫前期患者的基底板、绒毛膜绒毛和母血血清中PAPP-A2升高，但在脐血中检测不到。
PAPP-A2在不同的滋养层细胞群体中差异表达，在绒毛膜绒毛样本的孕中期显示出强烈的下调。子痫前期妊娠的母血血清和胎盘组织中PAPP-A2水平均升高。PAPP-A2水平不受分娩影响。此外，在脐血中检测不到PAPP-A2，这表明胎儿循环中未重现母血和胎盘PAPP-A2的变化。
