Pre-eclampsia and expression of heparin-binding EGF-like growth factor

Abstract

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.