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STOX1: Key player in trophoblast dysfunction underlying early onset preeclampsia with growth retardation.

van Dijk M, Oudejans CB - J Pregnancy (2010)

Bottom Line: The known upstream regulation and downstream effector genes of the transcription factor STOX1 are described.Finally, we propose a model in which we combine the cell type-specific and allele-specific effects of STOX1.This includes intrinsic effects (differential CpG island methylation) and extrinsic effects (regulation of effector genes).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Chemistry, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. m.vdijk@vumc.nl

ABSTRACT
Currently, only two preeclampsia susceptibility genes (ACVR2A, STOX1) have been identified within confirmed regions with significant genome-wide linkage, although many genetic screens in multiple populations have been performed. In this paper, we focus on the STOX1 gene. The epigenetic status of this gene is discussed explaining the maternal transmission of the STOX1 susceptibility allele observed in preeclamptic families. The known upstream regulation and downstream effector genes of the transcription factor STOX1 are described. Finally, we propose a model in which we combine the cell type-specific and allele-specific effects of STOX1. This includes intrinsic effects (differential CpG island methylation) and extrinsic effects (regulation of effector genes).

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Model of a villus with an extravillous trophoblast column invading the maternal decidua. Below this model, showing different cell types within and originating from a villus, a table shows the STOX1 methylation pattern observed or hypothesized to be found in the different cell types. YY: placenta homozygous for the Y-allele; HH: placenta homozygous for the H-allele; uu: both alleles are unmethylated; mm: both alleles are methylated; um: imprinting (only one allele is methylated).
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fig1: Model of a villus with an extravillous trophoblast column invading the maternal decidua. Below this model, showing different cell types within and originating from a villus, a table shows the STOX1 methylation pattern observed or hypothesized to be found in the different cell types. YY: placenta homozygous for the Y-allele; HH: placenta homozygous for the H-allele; uu: both alleles are unmethylated; mm: both alleles are methylated; um: imprinting (only one allele is methylated).

Mentions: In first trimester placenta, insufficient spiral artery remodeling is the fetal pathophysiological origin of preeclampsia [10]. In a normal pregnancy, extravillous trophoblasts from the fetal placenta invade the maternal decidua up to one-third of the myometrium (see also Figure 1). These trophoblasts are thereby transforming the maternal spiral arteries by replacing smooth muscle and elastic tissue with fibrinoid material changing them from low-capacity high-resistance into high-capacity low-resistance vessels. In preeclampsia, this extravillous trophoblast-directed spiral artery remodeling is incomplete leading to a decrease in placental blood flow, which subsequently leads to a response from the mother increasing her blood pressure. This in turn leads to maternal systemic failure giving rise to the maternal symptoms [10].


STOX1: Key player in trophoblast dysfunction underlying early onset preeclampsia with growth retardation.

van Dijk M, Oudejans CB - J Pregnancy (2010)

Model of a villus with an extravillous trophoblast column invading the maternal decidua. Below this model, showing different cell types within and originating from a villus, a table shows the STOX1 methylation pattern observed or hypothesized to be found in the different cell types. YY: placenta homozygous for the Y-allele; HH: placenta homozygous for the H-allele; uu: both alleles are unmethylated; mm: both alleles are methylated; um: imprinting (only one allele is methylated).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066643&req=5

fig1: Model of a villus with an extravillous trophoblast column invading the maternal decidua. Below this model, showing different cell types within and originating from a villus, a table shows the STOX1 methylation pattern observed or hypothesized to be found in the different cell types. YY: placenta homozygous for the Y-allele; HH: placenta homozygous for the H-allele; uu: both alleles are unmethylated; mm: both alleles are methylated; um: imprinting (only one allele is methylated).
Mentions: In first trimester placenta, insufficient spiral artery remodeling is the fetal pathophysiological origin of preeclampsia [10]. In a normal pregnancy, extravillous trophoblasts from the fetal placenta invade the maternal decidua up to one-third of the myometrium (see also Figure 1). These trophoblasts are thereby transforming the maternal spiral arteries by replacing smooth muscle and elastic tissue with fibrinoid material changing them from low-capacity high-resistance into high-capacity low-resistance vessels. In preeclampsia, this extravillous trophoblast-directed spiral artery remodeling is incomplete leading to a decrease in placental blood flow, which subsequently leads to a response from the mother increasing her blood pressure. This in turn leads to maternal systemic failure giving rise to the maternal symptoms [10].

Bottom Line: The known upstream regulation and downstream effector genes of the transcription factor STOX1 are described.Finally, we propose a model in which we combine the cell type-specific and allele-specific effects of STOX1.This includes intrinsic effects (differential CpG island methylation) and extrinsic effects (regulation of effector genes).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Chemistry, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. m.vdijk@vumc.nl

ABSTRACT
Currently, only two preeclampsia susceptibility genes (ACVR2A, STOX1) have been identified within confirmed regions with significant genome-wide linkage, although many genetic screens in multiple populations have been performed. In this paper, we focus on the STOX1 gene. The epigenetic status of this gene is discussed explaining the maternal transmission of the STOX1 susceptibility allele observed in preeclamptic families. The known upstream regulation and downstream effector genes of the transcription factor STOX1 are described. Finally, we propose a model in which we combine the cell type-specific and allele-specific effects of STOX1. This includes intrinsic effects (differential CpG island methylation) and extrinsic effects (regulation of effector genes).

Show MeSH
Related in: MedlinePlus