Functional evaluation of STOX1 in placentation, preeclampsia and preterm birth

Caroline E Dunk, Marie Van Dijk, Ruhul Choudhury, Thomas J. Wright, Brian Cox, Katherine Leavey, Lynda K Harris, Rebecca Jones, Stephen J. Lye

Research output: Contribution to journalArticlepeer-review


Revaluation of the association of the STOX1 transcription factor mutation (Y153H, C allele) with the early uterovascular origins of placental pathology is warranted. To investigate if placental STOX1 Y153H genotype affects uterovascular remodeling -compromised in both PTB and PE we utilised extravillous trophoblast (EVT) explant and placental decidual co-culture models, transfection of STOX1 wildtype and mutant plasmids into EVT-like trophoblast cell lines, and a cohort of 75 placentas from obstetric pathologies. Primary EVT and HTR8/SVneo cells carrying STOX1 Y153H secreted lower levels of IL6, and IL8, and higher CXCL16 and TRAIL than wildtype EVT and Swan71 cells. Media from wildtype EVT or Swan71 cells transfected with wildtype STOX1 stimulated: endothelial chemokine expression, angiogenesis and dNK and monocyte migration. In contrast, Y153H EVT conditioned medium, Swan71 transfected with the Y153H plasmid, or HTR8/SVneo media had no effect. Genotyping of placental decidual co cultures demonstrated association of the placental STOX1 CC allele with failed vascular remodeling. Decidual GG NODAL R165H increased in failed co-cultures carrying the placental CC alleles of STOX1. Multivariate analysis of the placental cohort showed that the STOX1 C allele correlated with premature birth, with or without severe early onset PE and SGA babies. In conclusion, placental STOX1 Y153H is a precipitating factor in preterm birth and placental PE due to defects in early uteroplacental development.
Original languageEnglish
Publication statusAccepted/In press - 24 Nov 2020


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