title: OS081. Novel KCNQ3/KCNE5 isoform protein and mRNA expression in first trimester human placentae.
abstract: BACKGROUND
  Potassium channel α-subunits encoded by KCNQ1-5 genes (Kv7) form voltage-dependent channels that can be modulated by KCNE1-5 encoded accessory proteins. These channels are known to play a role in the reactivity of blood vessels. We have previously shown that both mRNA and protein expression for the novel combination of KCNQ3 and KCNE5 are increased in term and preterm pre-eclampsia (PE) compared to normotensive control placentae [1]. The expression of these isoforms in early placental tissue has not been examined.
  
  
  OBJECTIVE
  The aims of this study were to determine whether KCNQ3 and KCNE5 mRNA and proteins are expressed in first trimester placental tissue.
  
  
  METHODS
  Placental samples were obtained from women undergoing elective surgical termination of pregnancy between 6 and 12 weeks' gestation (n=7) following informed written consent. KCNQ3 and KCNE5 mRNA expression was measured by qRT-PCR and normalised to stably expressed GAPDH. Immunohistochemistry was used to assess protein expression and localisation of the isoforms.
  
  
  RESULTS
  Both mRNA and protein expression of KCNQ3 and KCNE5 were detected in placental tissue at all gestations. KCNE5 mRNA expression remained constant between 6 and 10 weeks with a subsequent rise at 11 and 12 weeks. KCNQ3 mRNA expression was initially lower than KCNE5 but markedly increased at 7 weeks remaining high until 10 weeks and falling below KCNE5 levels by 12 weeks. Protein expression for both KCNQ3 and KCNE5 was localised mainly to the syncytiotrophoblast but was also evident in the mesenchyme; overall KCNQ3 intensity significantly increased with gestational age (p=0.044).
  
  
  CONCLUSIONS
  KCNQ3 and KCNE5 channel isoforms are highly expressed in first trimester placenta. The temporal changes in mRNA expression mirror changes in the placental tissue oxygen tension which increases between 8 and 10 weeks. This would precede the dislocation of the spiral artery plugs enabling maternal blood to flow freely and continuously into the intervillous spaces. We speculate that the increase in mesenchymal protein expression may be related to angiogenesis during this critical window of feto-placental vascular development. Future work will characterise the complete KCNQ/KCNE isoforms in first trimester placental tissue and assess potential functional roles of these channels both in early placentation and in relation to PE.
  
  
  BACKGROUND
  Tommy's Charity (Registered charity 1060508).
authors.affiliation: Women's Health, KIng's College London, United Kingdom.
authors.forename: H D
authors.initials: HD
authors.lastname: Mistry
authors.affiliation: Obstetrics & Gynaecology, University of Nottingham, Nottingham, United Kingdom.
authors.forename: L O
authors.initials: LO
authors.lastname: Kurlak
authors.affiliation: Biomedical Sciences, St. George's University of London, United Kingdom.
authors.forename: G S
authors.initials: GS
authors.lastname: Whitley
authors.affiliation: Biomedical Sciences, St. Geogre's University of London, United Kingdom.
authors.forename: J E
authors.initials: JE
authors.lastname: Cartwright
authors.affiliation: Women's Health, KIng's College London, United Kingdom.
authors.forename: R M
authors.initials: RM
authors.lastname: Tribe
authors.affiliation: Obstetrics & Gynaecology, University of Nottingham, Nottingham, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Broughton Pipkin