title: Activin signalling and pre-eclampsia: from genetic risk to pre-symptomatic biomarker.
abstract: Pre-eclampsia is a multi-system condition in pregnancy that is characterised by the onset of hypertension and proteinuria in women after the 20th week and it remains a leading cause of maternal and fetal mortality. Despite this the causative molecular basis of pre-eclampsia remains poorly understood. As a result, an intensive research effort has focused on understanding the molecular mechanisms involved in pre-eclampsia and using this information to identify new pre-symptomatic bio-markers of the condition. Activin A and its receptor, ACVR2A, have been extensively studied in this regard. Activin A is a member of the transforming growth factor (TGF)-β superfamily that has a wide range of biological functions depending on the cellular context. Recent work has shown that polymorphisms in ACVR2A may be a genetic risk factor for pre-eclampsia. Furthermore, both placenta and serum levels of Activin A are significantly increased in pre-eclampsia suggesting that Activin A may be a possible biomarker for the condition. Here we review the latest advances in this field and link these with new molecular data that suggest that the oxidative stress and pro-inflammatory cytokine production seen in pre-eclampsia may result in increased placental Activin A secretion in an attempt to maintain placental function.
authors.affiliation: Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland; Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland.
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Williamson
authors.affiliation: Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland; Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland. Electronic address: g.okeeffe@ucc.ie.
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
authors.affiliation: Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland; Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland. Electronic address: l.kenny@ucc.ie.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Kenny
mesh_terms: D028341:Activins / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012307:Risk Factors; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016212:Transforming Growth Factor beta; D028341:Activins
keywords: ACVR2A; Activin A; Biomarker; Pre-eclampsia; Serum