Leach Richard E, Romero Roberto, Kim Yeon Mee, Chaiworapongsa Tinnakorn, Kilburn Brian, Das Sanjoy K, Dey Sudhansu K, Johnson Anthony, Qureshi Faisal, Jacques Suzanne, Armant D Randall
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201-1415, USA.
Lancet. 2002 Oct 19;360(9341):1215-9. doi: 10.1016/S0140-6736(02)11283-9.
Pre-eclampsia is a disorder of pregnancy associated with poor extravillous cytotrophoblast invasion and above-normal rates of apoptosis in the trophoblast. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has strong cytoprotective activity and is an important signalling protein that regulates trophoblast invasion during early placentation. We aimed to establish whether HB-EGF expression is altered in placentae of pre-eclamptic women.
We assessed the expression of HB-EGF mRNA and protein by in-situ hybridisation and immunohistochemical techniques, respectively, in archived placental tissues from pregnancies terminated at around 20 weeks of gestation, and from women delivering between weeks 19 and 35 of gestation with preterm labour, small for gestational age infants, or pre-eclampsia.
HB-EGF mRNA and protein were expressed in villous and extravillous cytotrophoblast cells up to week 35 of gestation in placentae from women who delivered preterm. Similar levels of HB-EGF protein were found in the placentae of women who were not in labour. HB-EGF expression was reduced about five-fold (p=0.0001) in pre-eclamptic pregnancies. Fetal growth retardation, which has been linked with shallow trophoblast invasion and moderate apoptosis, was associated with placentae expressing intermediate levels of HB-EGF.
In pre-eclampsia, deficient HB-EGF signalling during placental development could impair trophoblast survival, differentiation, and invasion, leading to poor placental perfusion and hypertension.
子痫前期是一种妊娠相关疾病，与绒毛外细胞滋养层细胞浸润不良及滋养层细胞凋亡率高于正常水平有关。肝素结合表皮生长因子样生长因子（HB-EGF）具有强大的细胞保护活性，是早期胎盘形成过程中调节滋养层细胞浸润的重要信号蛋白。我们旨在确定子痫前期孕妇胎盘组织中HB-EGF的表达是否发生改变。
我们分别采用原位杂交和免疫组化技术，评估了妊娠约20周时终止妊娠的存档胎盘组织，以及妊娠19至35周间分娩的早产、小于胎龄儿或子痫前期孕妇的胎盘组织中HB-EGF mRNA和蛋白的表达。
在早产孕妇的胎盘中，直至妊娠35周时，HB-EGF mRNA和蛋白在绒毛和绒毛外细胞滋养层细胞中均有表达。未临产孕妇的胎盘组织中HB-EGF蛋白水平相似。子痫前期妊娠中HB-EGF表达降低约5倍（p=0.0001）。胎儿生长受限与滋养层细胞浸润浅和中度凋亡有关，与表达中等水平HB-EGF的胎盘有关。
在子痫前期，胎盘发育过程中HB-EGF信号不足可能损害滋养层细胞的存活、分化和浸润，导致胎盘灌注不良和高血压。
