Luchtvervuiling zwangerschap en zwangerschap Wilfried Gyselaers
Environ Health Perspect. 2005 Apr;113(4):375-82.
Genk Zuid 200 jongeren versus Vlaamse controle-groep Genk > Vl (p>0.05) Cadmium Lood Arseen Chroom Thallium Koper Hydroxypyreen Vlaams Humaan Biomonitoring-programma 2007-2011. Vlaamse Overheid, dienst Milieu & Gezondheid
Study: What is effect of in utero exposure to particulate air pollution on mtDNA + genome of placental tissue or cord blood
Studie 1
Hoeveelheid mtDNA ~ metabole activiteit vh weefsel
? (n Mitochondria ↑)
Methods
PM10 values: Krigin interpolation method Measuring stations interpolate air pollution levels to grids Validated model* * Janssen S et al. 2008. Spatial interpolation of air pollution measurements using CORINE land cover data. Atmospheric Environment 42:4884-4903.
2. Exposure measurements Distance to major roads (N-E road) Lifestyle factors: Questionnaire (e.g. smoking, diet, …)
mtDNA-content = mtDNA/nDNA 3. Measuring mitochondrial DNA-content in different matrices DNA extraction Real-time PCR mtDNA-content = mtDNA/nDNA
Results Linear regression analysis No association with umbilical cord blood
Multiple regression analysis Distance to major road is a surrogate for traffic related air pollution* * Hoek G et al. 2002. Association between mortality and indicators of traffic-related air pollution in the Netherlands: a cohort study. Lancet 360:1203-1209.
BIO-ENERGETIC DECLINE Mitochondrial DNA content Environmental components (PM, toxic metals) Mitochondrion ETC ROS ROS ENERGY COMPENSATION mtDNAcn Mitochondrial abundance ROS Mitochondrial dysregulation mtDNA mutation Feedback mechanism Lack of histones Insufficient DNA repair BIO-ENERGETIC DECLINE mtDNAcn Mitochondrial abundance
Epigenetische gen-modulatie Studie 2 DNA-methylatie Epigenetische gen-modulatie
Voorbeeld: maagkanker
Results
Besluit (1) Effecten van fijn stof vervuiling op placenta-DNA Mitochondriaal DNA daalt Hypo-methylatie genoom DNA-effecten treden op tijdens het ganse verloop van de zwangerschap
Besluit (2) Klinische effecten: Verlaagde foetale groei en toename IUGR, meest uitgesproken bij geboorte tussen 32 – 36w Lange termijn gezondheid als neonaat opgroeit tot kind of volwassene ?
Verdere studies BIRTH 2 year 5-7 year Adolescent ??? Polymorphisms Gene expression Arterial stiffness Asthma, wheezing … BIRTH 2 year 5-7 year Adolescent ???
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