Gestational Age-Dependent Extravillous Cytotrophoblast Osteopontin(OPN) Immunolocalization in the Basal Plate and Uteroplacental Vasculature Differentiates between Normal and Growth-Restricted Fetuses † 261

Abstract

Human placentation requires modulation of proliferative cytotrophoblasts to an invasive phenotype to create the intervillous space. Preeclampsia is characterized by failed trophoblast invasion and remodeling of the maternal spiral arteries. OPN is a secreted extracellular matrix protein found in many tissues including human trophoblast, and has been implicated in cell adhesion, invasion, spreading, and migration. To investigate gestational age-specific expression of OPN, immunohistochemical staining of post-partum placental tissue from 13 healthy women was performed using a monoclonal antibody against OPN (MPIIIB10-1). OPN protein was localized to the cytoplasm of invasive extravillous trophoblast from 24-28 wks (N=7). After 28 wks (N=6), OPN was undetectable in the extravillous trophoblast, and was not identified in non-invasive intravillous cytotrophoblast and syncytiotrophoblast at any gestational age (N=13). To investigate the role of OPN in uteroplacental vascular pathology, immunohistochemical staining of post-partum placentas from pregnancies complicated by preeclampsia (N=6) or intrauterine growth retardation (N=2) was performed using MPIIIB10-1 and compared to staining of placentas from gestational age-matched controls without pregnancy-induced maternal vascular disease (N=13). In the preecclampsia group, there was prominent proliferation of cytotrophoblast in the basal plate with intense OPN staining, in association with morphologic evidence of compromised uteroplacental perfusion. This staining pattern was identified in all preeclamptic placentas at 24-40 wks. In contrast, the normal and IUGR placentas did not display prominent cytotrophoblast proliferation or evidence of decreased uteroplacental perfusion: OPN staining was limited to the invasive extravillous cytotrophoblast and detected only until 28 wks. The data suggests a role for OPN in trophoblast invasion of the maternal vasculature and extracellular matrix during normal placentation, where OPN may serve as a marker for uteroplacental vascular remodeling in the human fetus. In the preeclamptic pregnancy, extravillous cytotrophoblast continues to express OPN even at advanced gestational ages, which supports the speculation that intervillous fibrin/fibrinoid may be actively involved in the remodeling of the intervillous space. OPN may be critical in this process, the successful maintenance of which may necessary for fetal compensation.