| 1. |
- Alavian-Ghavanini, Ali, et al.
(författare)
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Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ma, Ping, et al.
(författare)
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Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200â mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-Crossed D sign°[ and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50â mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects.
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| 3. |
- Repouskou, Anastasia, et al.
(författare)
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Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1st trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenita I distance (AGD) in their baby boys. Mice were treated with 0, 0.26, 2.6 and 13 mg/kg/d of the mixture, corresponding to 0x, 10x, 100x, 500x levels detected in the pregnant women. Adverse outcomes detected in the reproductive system of the offspring in pre-puberty and adulthood included reduced AGD index and gonadal weight, changes in gonadal histology and altered expression of key regulators of gonadal growth and steroidogenesis. Most aberrations were apparent in both sexes, though more pronounced in males, and exhibited a non-monotonic pattern. The phthalate mixture directly affected expression of steroidogenesis as demonstrated in a relevant in vitro model. The detected adversities at exposures close to the levels detected in pregnant women, raise concern on the existing safety limits for early-life human exposures and emphasizes the need for re-evaluation of the exposure risk.
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| 4. |
- Wikström, Sverre, et al.
(författare)
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Early pregnancy serum levels of perfluoroalkyl substances and risk of preeclampsia in Swedish women.
- 2019
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Ingår i: Scientific Reports. - : Springer. - 2045-2322. ; 9:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a major cause of maternal and fetal morbidity. Emerging research shows an association with environmental exposures. The present aim was to investigate associations between early pregnancy serum levels of perfluoroalkyl substances (PFAS) and preeclampsia. Within the Swedish SELMA study, eight PFAS were measured at median 10 gestational weeks and cases of preeclampsia were postnatally identified from registers. Associations between individual PFAS and preeclampsia were assessed, adjusting for parity, age, weight and smoking. Out of 1,773 women in the study group, 64 (3.6%), developed preeclampsia. A doubling of PFOS and PFNA exposure, corresponding to an inter-quartile increase, was associated with an increased risk for preeclampsia of about 38-53% respectively. Serum PFOS within the highest quartile was associated with an odds ratio of 2.68 (CI 95%: 1.17-6.12), equal to the increased risk associated with nulliparity, when compared to exposure in the first quartile. The same associations were identified, although with higher risk estimates, in analyses restricted to nulliparous women. For other PFAS, there were no associations. In conclusion and consistent with limited previous research only on PFOS, increasing serum levels of PFOS and PFNA during early pregnancy were associated with a clinically relevant risk of preeclampsia, adjusting for established confounders.
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