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- Lejonklou, Margareta Halin, 1966-, et al.
(författare)
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Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring.
- 2017
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 125:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.OBJECTIVES: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.METHODS: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to (BPA0.5; ) or (BPA50; ), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.RESULTS: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels ( compared with , females BPA50 ; compared with , males BPA0.5 ) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls ( number of adipocytes/HPF compared with number of adipocytes/HPF; ) and by 123% in BPA0.5 females compared with BPA50 animals ( number of adipocytes/high power field (HPF) compared with number of adipocytes/HPF; ). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals ( number of adipocytes/HPF compared with number of adipocytes/HPF; ). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.CONCLUSIONS: Developmental exposure to of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at were compared with the offspring of unexposed controls.
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| 2. |
- Lind, Thomas, et al.
(författare)
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Low-dose developmental exposure to bisphenol A induces sex-specific effects in bone of Fischer 344 rat offspring
- 2017
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 159, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bisphenol A (BPA) is a component of polycarbonate plastics to which humans are regularly exposed at low levels, and an endocrine disruptor with effects on several hormonal systems. Bone is a sensitive hormone target tissue, and we have recently shown that in utero and lactational exposure to 25µg BPA/kg BW/day alters femoral geometry in rat offspring.OBJECTIVE: To investigate bone effects in rat offspring after developmental exposure to a BPA dose in the range of human daily exposure (0.1-1.5µg/kg BW/day) as well as a dose to corroborate previous findings.METHODS: Pregnant Fischer 344 rats were exposed to BPA via drinking water corresponding to 0.5µg/kg BW/day: [0.5], (n=21) or 50µg/kg BW/day: [50], (n = 16) from gestational day 3.5 until postnatal day 22, while controls were given only vehicle (n = 25). The offspring was sacrificed at 5 weeks of age. Bone effects were analyzed using peripheral quantitative computed tomography (pQCT), the 3-point bending test, plasma markers of bone turnover, and gene expression in cortical bone and bone marrow.RESULTS: Compared to controls, male offspring developmentally exposed to BPA had shorter femurs. pQCT analysis revealed effects in the [0.5] group, but not in the [50] group; BPA reduced both trabecular area (-3.9%, p < 0.01) and total cross sectional area (-4.1%, p < 0.01) of femurs in the [0.5] group, whereas no effects were seen on bone density. Conversely, bone length and size were not affected in female offspring. However, the procollagen type I N-terminal propeptide (P1NP), a peptide formed during type 1 collagen synthesis, was increased in plasma (42%: p < 0.01) in female offspring exposed to [0.5] of BPA, although collagen gene expression was not increased in bone. The biomechanical properties of the bones were not altered in either sex. Bone marrow mRNA expression was only affected in male offspring.CONCLUSIONS: Developmental low-dose exposure to BPA resulted in sex-specific bone effects in rat offspring. A dose approximately eight times lower than the current temporary EFSA human tolerable daily intake of 4µg/kg BW/day, reduced bone length and size in male rat offspring. Long-term studies are needed to clarify whether the increased plasma levels of P1NP in female offspring reflect development of fibrosis.
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| 3. |
- Stubleski, Jordan, 1990-, et al.
(författare)
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The effect of drinking water contaminated with perfluoroalkyl substances on a 10-year longitudinal trend of plasma levels in an elderly Uppsala cohort
- 2017
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 159, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In 2012, drinking water contaminated with per- and polyfluoroalkyl substances (PFASs), foremost perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) at levels over 20ng/L and 40ng/L, respectively, was confirmed in Uppsala, Sweden.OBJECTIVES: We assessed how a longitudinally sampled cohort's temporal trend in PFAS plasma concentration was influenced by their residential location and determined the plausible association or disparity between the PFASs detected in the drinking water and the trend in the study cohort.METHODS: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort provided plasma samples three times from 2001 to 2014. Individuals maintaining the same zip code throughout the study (n = 399) were divided into a reference (no known PFAS exposure), low, intermediate and high exposure area depending on the proportion of contaminated drinking water received. Eight PFASs detected in the majority (75%) of the cohort's plasma samples were evaluated for significant changes in temporal PFAS concentrations using a random effects (mixed) model.RESULTS: PFHxS plasma concentrations continued to significantly increase in individuals living in areas receiving the largest percentage of contaminated drinking water (p < 0.0001), while PFOS showed an overall decrease. The temporal trend of other PFAS plasma concentrations did not show an association to the quality of drinking water received.CONCLUSIONS: The distribution of contaminated drinking water had a direct effect on the trend in PFHxS plasma levels among the different exposure groups, resulting in increased concentrations over time, especially in the intermediate and high exposure areas. PFOS and the remaining PFASs did not show the same relationship, suggesting other sources of exposure influenced these PFAS plasma trends.
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