Browsing by Subject "BPA"
Now showing items 1-4 of 4
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(2021)Objectives: Bisphenol A (BPA) is commonly used plasticizer that has endocrine disrupting properties. Fetal exposure to BPA has been associated with offspring behavioural problems. These associations may be mediated through BPA-induced alterations in the offspring DNA methylation (DNAm). This study examined whether fetal BPA exposure associates with behavioural problems and whether DNAm biomarker score for early pregnancy BPA exposure is linked with behavioural problems in the offspring. Methods: Participants were 442 mother-child pairs of the Finnish PREDO-cohort. I measured BPA from the early pregnancy urine samples and assayed DNAm in the cord blood with Illumina 450k or EPIC array. Mothers reported behavioural problems of their offspring with the Child Behaviour Checklist/1.5-5 (CBCL/1.5-5) at the mean child age of 3.8 years (SD = 1.0 years). I used LASSO regression to create a DNAm score for early pregnancy BPA exposure and tested the associations between BPA exposure, the DNAm score, and CBCL/1.5-5 scores with linear and logistic regressions. Results: After adjustments, early pregnancy BPA exposure was associated with higher risk for clinically meaningful internalizing (p = .02) and externalizing (p = .04) behavioural problems in the offspring. The DNAm score included eight CpG sites, explained 4.8% of the BPA variation, and was borderline significantly associated with a risk for clinically meaningful internalizing (p = .05) and externalizing behavioural problems (p = .06). Conclusions: Early pregnancy BPA exposure associated and DNAm biomarker for BPA exposure borderline associated with offspring behavioural problems. DNAm biomarker score for fetal BPA exposure showed promise and should be studied further in subsequent studies.
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(2021)Objectives: Bisphenol A (BPA) is commonly used plasticizer that has endocrine disrupting properties. Fetal exposure to BPA has been associated with offspring behavioural problems. These associations may be mediated through BPA-induced alterations in the offspring DNA methylation (DNAm). This study examined whether fetal BPA exposure associates with behavioural problems and whether DNAm biomarker score for early pregnancy BPA exposure is linked with behavioural problems in the offspring. Methods: Participants were 442 mother-child pairs of the Finnish PREDO-cohort. I measured BPA from the early pregnancy urine samples and assayed DNAm in the cord blood with Illumina 450k or EPIC array. Mothers reported behavioural problems of their offspring with the Child Behaviour Checklist/1.5-5 (CBCL/1.5-5) at the mean child age of 3.8 years (SD = 1.0 years). I used LASSO regression to create a DNAm score for early pregnancy BPA exposure and tested the associations between BPA exposure, the DNAm score, and CBCL/1.5-5 scores with linear and logistic regressions. Results: After adjustments, early pregnancy BPA exposure was associated with higher risk for clinically meaningful internalizing (p = .02) and externalizing (p = .04) behavioural problems in the offspring. The DNAm score included eight CpG sites, explained 4.8% of the BPA variation, and was borderline significantly associated with a risk for clinically meaningful internalizing (p = .05) and externalizing behavioural problems (p = .06). Conclusions: Early pregnancy BPA exposure associated and DNAm biomarker for BPA exposure borderline associated with offspring behavioural problems. DNAm biomarker score for fetal BPA exposure showed promise and should be studied further in subsequent studies.
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(2016)The field of stem cell research is hotter than ever, because still today, the goal for easily achievable stem cells for the use of tissue engineering and stem cell therapies, is yet to be achieved. Also, human stem cell based test systems are potential replacements of present animal test models. The ongoing obesity epidemic creates pressure for scientists to resolve the causes behind it. One way of approaching the problem, is the study of adipogenesis with the use of a in-vitro cell model. This have already been done for a while, with rodent based cell models, but the present study took the human obesity research a bit closer to its subject by using humane adipose tissue derived mesenchymal stem cells (hASC). Also, the adipogenic induction is executed with a human adipose tissue extract (ATE). Epidemiologically, the rise in obesity rates correlates at some level, with the occurrence of known endocrine disrupting chemicals in our environment. These include e.g. some pesticides and plasticizers, such as tributyltin (TBT), bis(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA). In the present study, the effects of a variety of concentrations, ranging from 50nM to 100µM of BPA, on ATE induced adipogenesis of hASCs, was studied. The accumulation of triglycerides - a key parameter for adipogenesis - is evaluated with the use of oil-red-o (ORO) staining and photometric measurements. A set of tests was executed to find out if BPA possesses adipogenic, synergistic or antiadipogenic properties in this particular test system. No significant antiadipogenic, nor synergistic effects were seen. Some antiadipogenic effects were seen throughout the study, but without any dose-dependence. This study also showed need for further development of the test. ORO staining needs to be further standardized to increase accuracy, different batches of ATE may cause variation in the results. All and all the test system is relatively easily modified and when fully functional, it is a great tool for screening for substances affecting our adipose tissue, and also for enhancing our knowledge on human adipogenesis in whole.
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(University of HelsinkiHelsingin yliopistoHelsingfors universitet, 2016)Hormonstörare är en samling hormonellt aktiva ämnen i vår närmiljö som påverkar hormonfunktionen i den grad att det leder till negativa hälsoeffekter. Incidensen för många hormonrelaterade sjukdomar har ökat i takt med vår ökade exponering för främmande kemikalier. Sjukdomarna är typiskt multifaktoriella som till exempel infertilitet, fetma, diabetes, hjärt- och kärlsjukdomar, bröstcancer och prostatacancer. Inom vetenskapen har en aktiv debatt gällande riskbedömningen av hormonstörarna pågått i årtionden. Syftet med detta licentiatarbete är att gå igenom en del av problematiken och presentera den på ett lättbegripligt sätt. Riskbedömningen har traditionellt lagt mest fokus på standardiserade toxikologiska studier men gällande hormonstörarna verkar testerna vara okänsliga. Trots att även icke-standardiserad (akademisk) forskning beaktas i riskbedömningen, läggs ofta större vikt vid de standardiserade studierna eftersom de uppfyller höga krav på tillförlitligheten. Plastmonomeren Bisfenol A används i en rad olika konsumentprodukter och har studerats ingående. Trots att den studerats mycket grundligt stöter den toxikologiska riskbedömningen hela tiden på nya problem. Hur man ska behandla resultat från mindre robusta studier där tidiga effekter upptäckts vid allt lägre doser är en omdebatterad fråga. Resultaten kan variera kraftigt beroende på vilken effekt man undersöker, till exempel en förändring i genexpression jämfört med organvikt. Därtill finns studier som tyder på en kraftigare effekt i kombination med andra kemikalier, något som den traditionella riskbedömningen inte tar i beaktande. Riskbedömningen är komplicerad eftersom exponeringsnivån är svår att uppskatta, det kan finnas kritiska tidpunkter för exponeringen och effekterna kan ha en lång latensperiod. Man har även kritiserat hur väl gnagare fungerar som modell för specifika sjukdomar hos människan, samt det kontroversiella fenomenet kring effekter vid lägre doser men inte vid högre, samt effekter vars dos-responskurva inte är monoton. De specifika mekanismerna för hormonstörare är till stor del okända och effekterna är svåra att förutspå, dessutom exponeras vi för en samling olika kemikalier vars sammansatta effekt är okänd. Den toxikologiska riskbedömningen står inför ett paradigmskifte inte minst när det gäller hormonstörarna. Förhoppningsvis kan arbetet vara till nytta som ett lättillgängligt informationspaket för människor med olika bakgrund och som vill sätta sig in i ämnet och följa med den pågående debatten.
Now showing items 1-4 of 4