Expression of eight glucocorticoid receptor isoforms in the human preterm placenta vary with fetal sex and birthweight

Introduction: Administration of betamethasone to women at risk of preterm delivery is known to be associated with reduced fetal growth via alterations in placental function and possibly direct effects on the fetus. The placental glucocorticoid receptor (GR) is central to this response and recent evidence suggests there are numerous isoforms for GR in term placentae. In this study we have questioned whether GR isoform expression varies in preterm placentae in relation to betamethasone exposure, fetal sex and birthweight. Methods: Preterm (24-36 completed weeks of gestation, n = 55) and term placentae (>37 completed weeks of gestation, n = 56) were collected at delivery. Placental GR expression was examined using Western Blot and analysed in relation to gestational age at delivery, fetal sex, birthweight and betamethasone exposure. Data was analysed using non-parametric tests. Results: Eight known isoforms of the GR were detected in the preterm placenta and include GR alpha (94 kDa), GR beta (91 kDa), GR alpha C (81 kDa) GR P (74 kDa) GR alpha (65 kDa), GR alpha D1-3 (50-55 kDa). Expression varied between preterm and term placentae with a greater expression of GR alpha C in preterm placentae relative to term placentae. The only sex differences in preterm placentae was that GR alpha D2 expression was higher in males than females. There were no alterations in preterm placental GR expression in association with betamethasone exposure. Discussion: GR alpha C is the isoform involved in glucocorticoid induced apoptosis and suggests that its predominance in preterm placentae may contribute to the pathophysiology of preterm birth. (C) 2015 Elsevier Ltd. All rights reserved.