A5078464806- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Prenatal Screening and Diagnostics
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Apelin-related biomedical research
- Reproductive System and Pregnancy
- MicroRNA in disease regulation
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Alzheimer's disease research and treatments
- Infant Health and Development
- Fetal and Pediatric Neurological Disorders
- Gestational Trophoblastic Disease Studies
- Child and Adolescent Psychosocial and Emotional Development
- Sleep and related disorders
- Neonatal Respiratory Health Research
- Genetic Syndromes and Imprinting
- Gastrointestinal motility and disorders
- Diabetes Management and Research
- Arctic and Antarctic ice dynamics
- Pituitary Gland Disorders and Treatments
- Biomarkers in Disease Mechanisms
- Sleep and Wakefulness Research
University of Amsterdam
2017-2023
Amsterdam University Medical Centers
2018-2023
Amsterdam UMC Location University of Amsterdam
1996-2018
Amsterdam UMC Location Vrije Universiteit Amsterdam
2007-2017
University of Zurich
2017
King's College London
2016
Leiden University Medical Center
2011-2014
University Medical Center
2012
Institute of Developmental Physiology
2012
Leiden University
1991-2011
Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE the leading cause fetal maternal morbidity mortality, its molecular etiology still unclear. Here, we show that ELABELA (ELA), an endogenous ligand apelin receptor (APLNR, or APJ), circulating hormone secreted by placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria elevated blood pressure due to defective placental angiogenesis....
Decreased sleep duration and/or impaired quality negatively influence glucoregulation. The aim of this study was to assess subjective characteristics in patients with type 1 diabetes, relate long-term glycaemic control and possible risk factors for sleep. We studied 99 adult diabetes (55 men, 44 women, 26.9 ± 1.2 years) age-, sex- BMI-matched non-diabetic controls. Subjective were assessed by validated questionnaires, i.e. Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale the Berlin...
By affected sib-pair linkage analysis of 24 families with pre-eclampsia, we confirm a susceptibility locus on chromosome 10q22.1 in Dutch females: multipoint non-parametric score 3.6 near marker D10S1432 was obtained. Haplotype showed parent-of-origin effect: maximal allele sharing the sibs found for maternally derived alleles all families, but not paternally alleles. As matrilineal inheritance suggests presence expressed imprinted genes, while imprinting operates predominantly...
By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation cell–cell adhesion protein α-T-catenin (CTNNA3). This is effectuated at crucial epithelial–mesenchymal transition proliferative into invasive extravillous trophoblast. STOX1–CTNNA3 interaction direct includes Akt-mediated phosphorylated control nucleo-cytoplasmic shuttling ubiquitin-mediated...
The HELLP syndrome is a pregnancy-associated disease inducing hemolysis, elevated liver enzymes, and low platelets in the mother. Although symptoms occur third trimester mother, origin of can be found first fetal placenta. A locus for present on chromosome 12q23 near PAH. Here, by multipoint nonparametric linkage, pedigree structure allele sharing, haplotype association analysis affected sisters cousins, we demonstrate that an intergenic region 12q23.2 between PMCH IGF1. We identified novel...
Fatigue and excessive sleepiness have been reported after treatment of nonfunctioning pituitary macroadenomas (NFMA). Because these complaints may be caused by disturbed nocturnal sleep, we evaluated objective sleep characteristics in patients treated for NFMA.We conducted a controlled cross-sectional study.We studied 17 (8 women; mean age, 54 yr) remission NFMA during long-term follow-up yr; range, 1-18 surgery (n = 17) additional radiotherapy 5) without comorbidity except hypopituitarism...
Fetal trophoblast cells obtained noninvasively early in gestation provided fetal DNA for comprehensive targeted sequencing across the genome.
Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective function may result in severe pregnancy complications, including fetal growth restriction pre-eclampsia. The incidence of these complications is increased pregnancies fetuses affected by Rubinstein–Taybi syndrome, a developmental disorder predominantly caused heterozygous mutations CREB-binding protein ( CREBBP ) or E1A-binding p300 EP300 )....
Multiple sclerosis (MS) is a demyelinating and degenerative disease of the central nervous system. Normally, demyelination followed by remyelination, which requires repopulation demyelinated area oligodendrocyte precursor cells. Although large numbers cells are present in MS lesions, remyelination often fails, part inability to differentiate into mature myelin-forming In mouse rat, miR-219 required for this differentiation. Previously, we identified decreased expression tissue patients...
STOX1A is a transcription factor which functionally and structurally similar to the forkhead box protein family. has been shown be associated with pre-eclampsia, pregnancy disease, have potential implications in late onset Alzheimer's disease. However, exact function of its target genes are still largely unknown. Therefore, this study we performed chromatin immunoprecipitation coupled shotgun cloning discover novel genes. Our results show that CNTNAP2, member neurexin family, directly...
Pre-eclampsia and late-onset Alzheimer's disease (LOAD) share no clinical features. In contrast to these dissimilarities, striking parallels exist between the (epi)genetic features associated with pre-eclampsia LOAD for genes located
Saccharomyces cerevisiae contains three nonessential genes (NGL1, NGL2, and NGL3) that encode proteins containing a domain with similarity to Mg(2+)-dependent endonuclease motif present in the mRNA deadenylase Ccr4p. We have investigated possible role of these rRNA processing, because for many pre-rRNA processing steps, identity responsible nuclease remains elusive. Analysis RNA isolated from cells which NGL2 gene has been inactivated (ngl2delta) demonstrates correct 3'-end formation 5.8S at...
ABSTRACT Infection of mice with murine gammaherpesvirus 68 (MHV-68) is a well-characterized small animal model for the study infection. MHV-68 belongs to same herpesvirus family as saimiri (HVS) New World squirrel monkeys and human 8 (HHV-8) (also referred Kaposi's sarcoma-associated [KSHV]). The open reading frame ORF74 HVS, KSHV, encodes protein homology G protein-coupled receptors chemokine in particular. KSHV (human [hORF74]) highly constitutively active has been implicated pathogenesis...
LINC-HELLP, showing chromosomal linkage with the pregnancy-specific HELLP syndrome in Dutch families, reduces differentiation from a proliferative to an invasive phenotype of first-trimester extravillous trophoblasts. Here we show that mutations LINC-HELLP identified families negatively affect this trophoblast either by inducing proliferation rate or causing cell cycle exit as shown decrease both and invasion. As LincRNAs predominantly function through interactions proteins, directly...
The 10q22 chromosomal region with genomic linkage to pre-eclampsia in Dutch females shows a parent-of-origin effect maternal transmission of the Y153H susceptibility allele STOX1 gene. Although CpG island within promoter no differential methylation, this study describes identification differentially methylated (DMR) intron 1 Methylation coincides expression, where high methylation leads reduced expression. In SGHPL-5 extravillous trophoblast cell line allele-specific expression was observed...
Abstract Preeclampsia is a frequent gestational hypertensive disorder with equivocal pathophysiology. Knockout of peptide hormone ELABELA (ELA) has been shown to cause preeclampsia-like symptoms in mice. However, the role ELA human placentation and whether involved development preeclampsia humans not yet known. In this study, we show that exogenous administration able increase invasiveness extravillous trophoblasts vitro , change outgrowth morphology reduce trophoblast proliferation ex vivo...
Background In this study we investigated the involvement of transcription factor STOX1A in regulation cell cycle. Methodology/Principal Findings We found that several major cycle regulatory genes were differentially expressed upon stimulation and knockdown neuroblastoma line SH-SY5Y. This includes dependent differential cyclin B1 expression, a which is known to regulate mitotic entry during The expression by direct as shown with chromatin immunoprecipitation. Results furthermore suggest...
Revaluation of the association STOX1 (STORKHEAD_BOX1 PROTEIN 1) transcription factor mutation (Y153H, C allele) with early utero-vascular origins placental pathology is warranted. To investigate if Y153H genotype affects remodeling—compromised in both preterm birth and preeclampsia—we utilized extravillous trophoblast (EVT) explant decidual coculture models, transfection wild-type mutant plasmids into EVT-like cell lines, a cohort 75 placentas from obstetric pathologies. Primary EVT...
The constitutively active G-protein-coupled receptor and viral oncogene ORF74, encoded by Kaposi sarcoma-associated herpesvirus (human 8), binds a broad range of chemokines, including CXCL1 (agonist), CXCL8 (neutral ligand), CXCL10 (inverse agonist). Although chemokines interact with the extracellular N terminus loops receptor, we demonstrate that helix 8 (Hx8) in intracellular carboxyl tail (C-tail) ORF74 directs chemokine binding. Partial deletion C-tail resulted phenotype reduced...