Background: Potassium channel α-subunits encoded by KCNQ1-5 genes (Kv7) form voltage-dependent channels which can be modulated by KCNE1-5 encoded accessory proteins. These channels are known to play a role in regulating the reactivity of blood vessels. We have previously shown that both mRNA and protein data indicates a novel combination of KCNQ3 and KCNE5 expression in placentae from preterm and term pre-eclampsia; the expression of these specific KCNQ and KCNE isoforms in early placental tissue remains to be elucidated. Objectives: The aims of this study were to determine whether KCNQs and KCNEs mRNA are expressed in first trimester placental tissue and to assess protein expression and localisation of the KCNQ3 and KCNE5 isoforms. Methods: Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at ≤10 weeks’ (early TOP; n=6) and >10 weeks’ (late TOP; n=7) gestations following informed written consent. Expression of mRNA for all KNNQ and KCNE isoforms were measured by qRT-PCR and normalised to three housekeeper genes using geNorm. Protein localisation/expression of KCNQ3 and KCNE5 were assessed by immunohistochemistry. Results: Expression of mRNA (normalised copy number) of both all KCNQs and KCNEs were observed at all gestations. KCNE5 expression (median [IQR]) was increased in late TOP (239.5 [135, 305]) versus early TOP samples (77.6 [57.5, 111.8], P=0.01). No other significant differences were detected for other KCNQ and KCNE genes (P>0.05). KCNE5 mRNA expression remained constant between 6 and 10 weeks’ (median: 77.6) with a subsequent rise at 11 and 12 weeks’ and a larger increase after 13 weeks’ (median: 239.5). KCNQ3 mRNA expression was initially lower than KCNE5, but increased at 10 weeks (median: 153.1) and then fell below KCNE5 vales by 12 weeks’ (median: 22.3). Protein expression for both isoforms was localised predominantly to the syncytiotrophoblast with some expression in the mesenchyme. Conclusion: KCNQ3 and KCNE5 channel isoforms are highly expressed in first trimester human placenta. The changes in mRNA expression mirror temporal changes in the placental tissue oxygen tension which increases between 8-10 weeks’. This precedes the dislocation of the spiral artery plugs, which enables maternal blood to flow freely and continuously into the intervillous spaces. We speculate that mesenchymal protein expression may be related to angiogenesis during this critical window of feto-placental vascular development. We will perform functional studies to determine the potential role of this channel complex in the syncytiotrophoblast. Future work will characterise the complete KCNQ/KCNE profile in first trimester tissue and assess their potential functional roles both in early placentation and in relation to pre-eclampsia. Funding: Nottingham Hospital Special Trustees (No: 1053904).