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Linking genotype to trophoblast phenotype in preeclampsia and HELLP syndrome associated with STOX1 genetic variants

Linking genotype to trophoblast phenotype in preeclampsia and HELLP syndrome associated with STOX1 genetic variants

Authors :
Lorenzo Costa
Luis Bermudez-Guzman
Ikram Benouda
Paul Laissue
Adrien Morel
Karen Marcela Jiménez
Thierry Fournier
Laurence Stouvenel
Céline Méhats
Francisco Miralles
Daniel Vaiman
Source :
iScience, Vol 27, Iss 3, Pp 109260- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Preeclampsia is a major hypertensive pregnancy disorder with a 50% heritability. The first identified gene involved in the disease is STOX1, a transcription factor, whose variant Y153H predisposes to the disease. Two rare mutations were also identified in Colombian women affected by the hemolysis, elevated liver enzyme, low platelet syndrome, a complication of preeclampsia (T188N and R364X). Here, we explore the effects of these variants in trophoblast cell models (BeWo) where STOX1 was previously invalidated. We firstly showed that STOX1 knockout alters response to oxidative stress, cell proliferation, and fusion capacity. Then, we showed that mutant versions of STOX1 trigger alterations in gene profiles, growth, fusion, and oxidative stress management. The results also reveal alterations of the STOX interaction with DNA when the mutations affected the DNA-binding domain of STOX1 (Y153H and T188N). We also reveal here that a major contributor of these effects appears to be the E2F3 transcription factor.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
3
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.b911a702ca1a4fb291a95d0fd611069d
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.109260