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Stubleski, J., Kukucka, P., Salihovic, S., Lind, P. M., Lind, L. & Kärrman, A. (2018). A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction. Journal of Chromatography A, 1546, 18-27, Article ID S0021-9673(18)30253-X.
Open this publication in new window or tab >>A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1546, p. 18-27, article id S0021-9673(18)30253-XArticle in journal (Refereed) Published
Abstract [en]

The objective of this study was to develop and validate a 96-well plate solid phase extraction method for analysis of 23 lipophilic persistent organic pollutants (POPs) in low-volume plasma and serum samples which is applicable for biomonitoring and epidemiological studies. The analysis of selected markers for internal exposure: 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and polybrominated diphenylether 47 (BDE 47) was evaluated by comparing two SPE sorbents and GC-HRMS or GC-MS/MS detection. The final method extracted 23 POPs from 150 μL of serum and plasma using a 96-well extraction plate containing 60 mg Oasis HLB sorbent per well prior to GC-HRMS magnetic sector analysis. The extraction method was applied to 40 plasma samples collected for an epidemiological study. The recovery of selected POPs ranged from 31% to 63% (n = 48), and detection limits ranged from 2.2 to 45 pg/mL for PCBs, 4.2 to 167 pg/mL for OCPs, 7.8 pg/mL for OCDD and 6.1 pg/mL for BDE 47. This method showed good precision with relative standard deviations of selected POP concentrations in quality control samples (n = 48) ranging from 11% to 25%. The trueness was determined with standard reference material serum (n = 48) and the deviation from certified values ranged from 1 to 27%. Of the 23 POPs analyzed, 18 were detected in 43% to 100% of plasma samples collected for the epidemiological study. The method showed good robustness with low inter-well plate variation (11-31%) determined by twelve 96-well plate extractions, and can extract 96 samples, including quality controls and procedural blanks in 2-3 days. Comparison with GC-MS/MS analysis showed that similar concentrations (within 0.5% to 30%) of most POPs could be obtained with GC-APCI-MS/MS. Larger deviations were observed for PCB 194 (60%) and trans-nonachlor (43%). The developed method produces accurate concentrations of low-level marker POPs in plasma and serum, providing a suitable high-throughput sample preparation procedure for biomonitoring and epidemiological studies involving large sample size and limited sample volume. GC-HRMS was chosen over GC-MS/MS, however the latter showed promising results, and could be used as an alternative to GC-HRMS analysis for most POPs.

Keywords
APCI-MS/MS, GC-HRMS, High-throughput SPE, Persistent organic pollutants
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348564 (URN)10.1016/j.chroma.2018.02.057 (DOI)000430766800003 ()29510870 (PubMedID)
Funder
Swedish Research Council Formas, 216-2013-478
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-06-26Bibliographically approved
Salihovic, S., Stubleski, J., Kärrman, A., Larsson, A., Fall, T., Lind, L. & Lind, P. M. (2018). Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study. Environment International, 117, 196-203
Open this publication in new window or tab >>Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, p. 196-203Article in journal (Refereed) Published
Abstract [en]

Background: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

Objective: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

Methods: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

Results: The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers beta(BILIRUBIN) = -1.56, 95% confidence interval (CI) -1.93 to -1.19, beta(ALT)= 0.04, 95% CI 0.03-0.06, and beta(ALP)= 0.11, 95% CI 0.06-0.15.

Conclusion: Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2018
Keywords
Epidemiology, Liver function markers, PFAS, ALT, Bilirubin, PFNA
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-361035 (URN)10.1016/j.envint.2018.04.052 (DOI)000436573400023 ()29754000 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047Swedish Research Council Formas, 2013-478Swedish Research Council Formas, 2015-756
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved
Lind, P. M., Salihovic, S., Stubleski, J., Kärrman, A. & Lind, L. (2018). Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study. Environmental health, 17, Article ID 59.
Open this publication in new window or tab >>Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study
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2018 (English)In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, article id 59Article in journal (Refereed) Published
Abstract [en]

Background: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.

Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.

Results: IMT increased 0.058 mm during the 10-year period (p <0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p <0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.

Conclusion: The change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Atherosclerosis, Longitudinal, Perfluoroalkyl substances (PFASs), Elderly, Epidemiology, IMT
National Category
Cardiac and Cardiovascular Systems Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-360187 (URN)10.1186/s12940-018-0403-0 (DOI)000437299700002 ()29970113 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2018-09-13Bibliographically approved
Mobacke, I., Lind, L., Dunder, L., Salihovic, S. & Lind, P. M. (2018). Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.. Environment International, 115, 295-300
Open this publication in new window or tab >>Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 115, p. 295-300Article in journal (Refereed) Published
Abstract [en]

AIMS: Some persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and some polychlorinated biphenyls (PCBs) have been shown to interfere with myocardial function and geometry. We therefore investigated if also another group of POPs: per- and polyfluoroalkyl substances (PFASs) were associated with alterations in left ventricular geometry.

METHODS: 801 subjects aged 70 years were investigated in a cross-sectional study within the scope of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants´ plasma by ultra-performance liquid chromatograph/tandem mass spectrometry. Left ventricular geometry was determined by echocardiography. Multivariable linear regression was used to investigate the associations between PFASs and left ventricular geometry of the heart after exclusion of subjects with previous myocardial infarction (n = 72).

RESULTS: When adjusting for multiple comparisons, none of the eight PFASs evaluated were significantly related to left ventricular mass. However, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were related to relative wall thickness (RWT) in a negative fashion (p < 0.0021). Besides being inversely related to RWT, PFNA was also positively related to left ventricular end-diastolic volume (LVEDD) (p < 0.0021). These analyses were adjusted for traditional cardiovascular risk factors.

CONCLUSION: In this cross-sectional study, several of the PFASs evaluated, especially PFNA, were related to myocardial geometry: a reduction in relative wall thickness and an increase in left ventricular diameter following adjustment for traditional cardiovascular risk factors, suggesting a role for PFASs in cardiac remodeling.

Keywords
Elderly, Environmental contaminants, Heart, Left ventricular geometry, Per- and polyfluoroalkyl substances (PFASs), Perfluorononanoic acid (PFNA)
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348565 (URN)10.1016/j.envint.2018.03.033 (DOI)000432523500032 ()29621717 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-08-20Bibliographically approved
Lind, P. M. & Lind, L. (2018). Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review. Diabetologia, 61(7), 1495-1502
Open this publication in new window or tab >>Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review
2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 7, p. 1495-1502Article, review/survey (Refereed) Published
Abstract [en]

The purpose of this study was to review the epidemiological and experimental evidence linking background exposure to a selection of environmental endocrine-disrupting chemicals (EDCs) with diabetes and impaired glucose metabolism. The review summarises the literature on both cross-sectional and prospective studies in humans, as well as experimental in vivo and in vitro studies. The findings were subjected to evidence grading according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. We found > 40 cross-sectional and seven prospective studies regarding EDCs and risk of diabetes. Taken together, there is moderate evidence for a relationship between exposure to dichlorodiphenyldichloroethylene (p,p'-DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane, and diabetes development. Regarding polychlorinated biphenyls (PCBs), it is likely that the rodent models used are not appropriate, and therefore the evidence is poorer than for p,p'-DDE. For other EDCs, such as bisphenol A, phthalates and perfluorinated chemicals, the evidence is scarce, since very few prospective studies exist. Brominated flame retardants do not seem to be associated with a disturbed glucose tolerance. Thus, evidence is accumulating that EDCs might be involved in diabetes development. Best evidence exists for p,p'-DDE. For other chemicals, both prospective studies and supporting animal data are still lacking.

Keywords
Bisphenol A, BPA, Chemicals, DDE, DDT, Diabetes, EDCs, Endocrine-disrupting chemicals, Pesticides, Review
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-365120 (URN)10.1007/s00125-018-4621-3 (DOI)000434250500001 ()29744538 (PubMedID)
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Lind, P. M., Salihovic, S. & Lind, L. (2018). High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis. Environment International, 113, 109-113
Open this publication in new window or tab >>High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis
2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 109-113Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Biological age, Epidemiology, Methylation, Organochlorine pesticides (OCPs), Transnonachlor, p, p′-DDE
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348563 (URN)10.1016/j.envint.2018.01.019 (DOI)000428976700013 ()29421399 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047 942-2015-756 216-2013-478
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-06-05Bibliographically approved
Stubleski, J., Lind, L., Salihovic, S., Lind, P. M. & Kärrman, A. (2018). Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women. Environmental Research, 165, 193-200
Open this publication in new window or tab >>Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women
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2018 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 165, p. 193-200Article in journal (Refereed) Published
Abstract [en]

Background: Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed. Objective: The objectives of this study are to examine the five year longitudinal trend in chlorinated and bro-minated (Cl/Br) POP concentrations in a sample of elderly individuals and to investigate the relationship between gender, changes in body weight, plasma lipid levels and POP concentrations. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, plasma samples were collected from the same individuals over a 5 year period. Originally 992 subjects (all aged 70) were sampled between 2001 and 2004 and 814 returning subjects (all aged 75) were sampled again from 2006 to 2009. Plasma concentrations of 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and one polybrominated diphenylether (BDE 47) were determined using high-throughput 96-well plate solid phase extraction and gas chromatography-high resolution mass spectrometry (GC-HAMS). Results: During the 5-year follow-up, plasma concentrations of all POPs significantly decreased (p < 0.00001). Median reductions ranged from 4% (PCB105) to 45% (PCB 99), with most reductions being in the 30-40% range. For most POPs, a larger decline was seen in men than in women. The relationship between the weight change and change in POP concentrations was generally negative, but a positive relationship between lipid levels and POP concentrations when expressed as wet-weight was observed. In general, similar changes in POP concentrations and their relationships to body weight were observed regardless of using either wet-weight (pg/ mL) or lipid-normalized (ng/g lipid) concentrations. Conclusion: In this longitudinal cohort study, gender and minor, but varying changes in body weight and lipid levels greatly influenced the individual-based changes in POP concentrations. In general, our findings suggest that men and women with larger decreases in body weight and greater increases in lipid levels have the slowest decline in body burden of POPs. Based on the results from this study, either wet-weight or lipid normalized concentrations can be used to determine the percent change in POP concentrations and their relationships to physiological changes and differences.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018
Keywords
Persistent organic pollutants, Longitudinal trend, PIVUS cohort, Body weight, Plasma lipids
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-361258 (URN)10.1016/j.envres.2018.04.009 (DOI)000437551200021 ()29715601 (PubMedID)
Funder
Swedish Research Council, K2009-64X-21031-01-3Swedish Research Council Formas, 216-2007-2047
Available from: 2018-10-11 Created: 2018-10-11 Last updated: 2018-10-11Bibliographically approved
Dunder, L., Lejonklou, M. H., Lind, L., Risérus, U. & Lind, P. M. (2018). Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring. Environmental Research, 166, 117-129
Open this publication in new window or tab >>Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring
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2018 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 166, p. 117-129Article in journal (Refereed) Published
Abstract [en]

Background. Bisphenol A (BPA) is an endocrine disruptor and also a suggested obesogen and metabolism-disrupting chemical. Accumulating data indicates that the fatty acid (FA) profile and their ratios in plasma and other metabolic tissues are associated with metabolic disorders. Stearoyl-CoA desaturase 1 (SCD-1) is a key regulator of lipid metabolism and its activity can be estimated by dividing the FA product by its precursor measured in blood or other tissues. Objective: The primary aim of this study was to investigate the effect of low-dose developmental BPA exposure on tissue-specific FA composition including estimated SCD-1 activity, studied in 5- and 52-week (wk)-old Fischer 344 (F344) rat offspring. Methods: Pregnant F344 rats were exposed to BPA via their drinking water corresponding to 0: [CTRL], 0.5: [BPA0.5], or 50 mu g/kg BW/day: [BPA50], from gestational day 3.5 until postnatal day 22. Results: BPA0.5 increased SCD-16 (estimated as the 16:1n-7/16:0 ratio) and SCD-18 (estimated as the 18:1n-9/ 18:0 ratio) indices in inguinal white adipose tissue triglycerides (iWAT-TG) and in plasma cholesterol esters (PL-CE), respectively, in 5-wk-old male offspring. In addition, BPA0.5 altered the FA composition in male offspring, e.g. by decreasing levels of the essential polyunsaturated FA linoleic acid (18:2n-6) in iWAT-and liver-TG. No differences were observed regarding the studied FAs in 52-wk-old offspring, although a slightly increased BW was observed in 52-wk-old female offspring. Conclusions: Low-dose developmental BPA exposure increased SCD-16 in iWAT-TG and SCD-18 in PL-CE of male offspring, which may reflect higher SCD-1 activity in these tissues. Altered desaturation activity and signs of altered FA composition are novel findings that may indicate insulin resistance in the rat offspring. These aforementioned results, together with the observed increased BW, adds to previously published data demonstrating that BPA can act as a metabolism disrupting chemical.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
BPA, Bisphenol A, Metabolism disrupting chemical, Low-dose exposure, FA, Fatty acid, SCD-1, Stearoyl-CoA desaturase 1, Adipose tissue
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-363414 (URN)10.1016/j.envres.2018.05.023 (DOI)000445318200016 ()29885613 (PubMedID)
Funder
Swedish Research Council Formas, 216-2012-475
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2018-10-18Bibliographically approved
Lee, D.-H., Porta, M., Lind, L., Lind, P. M. & Jacobs, D. R. (2018). Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia. Neurology, 90(4), 176-182
Open this publication in new window or tab >>Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia
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2018 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 4, p. 176-182Article in journal (Refereed) Published
Abstract [en]

Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.

National Category
Occupational Health and Environmental Health Neurosciences
Identifiers
urn:nbn:se:uu:diva-348561 (URN)10.1212/WNL.0000000000004851 (DOI)000427799500018 ()29358509 (PubMedID)
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-05-31Bibliographically approved
Alavian-Ghavanini, A., Lin, P.-I., Lind, P. M., Rimfors, S. R., Lejonklou, M. H., Dunder, L., . . . Rueegg, J. (2018). Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans. Scientific Reports, 8, Article ID 11315.
Open this publication in new window or tab >>Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 11315Article in journal (Refereed) Published
Abstract [en]

Bisphenol A (BPA) exposure has been linked to neurodevelopmental disorders and to effects on epigenetic regulation, such as DNA methylation, at genes involved in brain function. High doses of BPA have been shown to change expression and regulation of one such gene, Grin2b, in mice. Yet, if such changes occur at relevant doses in animals and humans has not been addressed. We investigated if low-dose developmental BPA exposure affects DNA methylation and expression of Grin2b in brains of adult rats. Furthermore, we assessed associations between prenatal BPA exposure and Grin2b methylation in 7-year old children. We found that Grin2b mRNA expression was increased and DNA methylation decreased in female, but not in male rats. In humans, prenatal BPA exposure was associated with increased methylation levels in girls. Additionally, Iow APGAR scores, a predictor for increased risk for neurodevelopmental diseases, were associated with higher Grin2b methylation levels in girls. Thus, we could link developmental BPA exposure and Iow APGAR scores to changes in the epigenetic regulation of Grin2b, a gene important for neuronal function, in a sexual dimorphic fashion. Discrepancies in exact locations and directions of the DNA methylation change might reflect differences between species, analysed tissues, exposure level and/or timing.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-361996 (URN)10.1038/s41598-018-29732-9 (DOI)000439965200008 ()30054528 (PubMedID)
Funder
EU, Horizon 2020, 634880Swedish Research Council, 216-2012-475Swedish Research Council, 210-2012-1502Swedish Research Council, 216-2013-1966
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8949-3555

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