TY - JOUR
T1 - Linking genotype to trophoblast phenotype in preeclampsia and HELLP syndrome associated with STOX1 genetic variants
AU - Costa, Lorenzo
AU - Bermudez-Guzman, Luis
AU - Benouda, Ikram
AU - Laissue, Paul
AU - Morel, Adrien
AU - Jiménez, Karen Marcela
AU - Fournier, Thierry
AU - Stouvenel, Laurence
AU - Méhats, Céline
AU - Miralles, Francisco
AU - Vaiman, Daniel
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/3/15
Y1 - 2024/3/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.isci.2024.109260
DO - 10.1016/j.isci.2024.109260
M3 - Research Article
C2 - 38439971
AN - SCOPUS:85188220941
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 3
M1 - 109260
ER -