Prenatal exposure to bisphenols and cognitive function in children at 7 years of age in the Swedish SELMA study

Bornehag, Carl‐Gustaf; Engdahl, Elin; Hallerbäck, Maria Unenge; Wikström, Sverre; Lindh, Christian; Rüegg, Joëlle; Tanner, Eva M.; Gennings, Chris

doi:10.1016/j.envint.2021.106433

Cited by 36 publications

(20 citation statements)

References 62 publications

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“…The most produced bisphenol is bisphenol A (BPA), but the use of structural analogues, such as bisphenol F (BPF) and bisphenol S (BPS), is increasing to substitute BPA in different products. The ubiquitous use of these chemicals can be reflected by their detection in urine [ 21 , 22 , 23 , 24 , 25 ] and brain [ 26 ] of most adults, as well as in umbilical cord blood [ 27 ]. Exposure to bisphenols has been shown to affect, for example, neurodevelopment in many animal studies [ 28 ], and epidemiological studies are supporting these experimental findings.…”

Section: Introductionmentioning

confidence: 99%

“…Exposure to bisphenols has been shown to affect, for example, neurodevelopment in many animal studies [ 28 ], and epidemiological studies are supporting these experimental findings. For example, prenatal BPA exposure has been repeatedly associated with changes in child neurobehavior [ 29 ], and prenatal BPF exposure has been associated with lower cognition in childhood [ 22 ]. In addition, rats exposed to BPA in utero displayed disrupted expression of genes involved in Alzheimer’s disease [ 30 ], and rat brain capillaries exposed to BPA ex vivo showed a decreased BCRP function [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

Engdahl

Schijndel

Voulgaris

et al. 2021

IJMS

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The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA’s known impact on neurodevelopment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

Engdahl

Schijndel

Voulgaris

et al. 2021

IJMS

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“…Investigations of memory functions in adult rodent offspring of both sexes perinatally exposed to one of the three chemicals show a heterogeneous picture with effects only in males or females, or differential or similar effects in males and females ( Supplementary Table S1 ). In children, two studies reported a link between prenatal bisphenol A exposure and preferential impairment of cognitive functions in boys ( Braun et al, 2017 ; Bornehag et al, 2021 ). A higher susceptibility of boys has also been observed with respect to other types of behaviors in relation to prenatal phthalate exposure ( Engel et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

“…The development of cognitive and emotional behaviors represents one of the best documented targets of endocrine disrupting chemicals (EDCs) in humans ( Boucher et al, 2009 ; Rauh et al, 2011 ; Braun et al, 2017 ; Ejaredar et al, 2017 ; Bornehag et al, 2021 ). Effects on learning and memory and on anxiety have been observed as well in rodent models, for example after perinatal exposure to bisphenol A ( Kubo et al, 2001 ; Ryan and Vandenbergh, 2010 ; Xu et al, 2010 , 2012 ; Jašarevic et al, 2011 ; Matsuda et al, 2013 ; Kumar and Thakur, 2014 ; Johnson et al, 2016 ), polychlorinated biphenyls (PCBs) ( Gilbert et al, 2000 ; Roegge et al, 2000 ; Widholm et al, 2001 ; Sugawara et al, 2006 ; Colciago et al, 2009 ), or phthalates ( Zhao et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

et al. 2021

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Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate <0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions.

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“…The development of cognitive and emotional behaviors represents one of the best documented targets of endocrine disrupting chemicals (EDCs) in humans (Boucher et al, 2009;Rauh et al, 2011;Braun et al, 2017;Ejaredar et al, 2017;Bornehag et al, 2021). Effects on learning and memory and on anxiety have been observed as well in rodent models, for example after perinatal exposure to bisphenol A (Kubo et al, 2001;Ryan and Vandenbergh, 2010;Xu et al, 2010Xu et al, , 2012Jašarevic et al, 2011;Matsuda et al, 2013;Kumar and Thakur, 2014;Johnson et al, 2016), polychlorinated biphenyls (PCBs) (Gilbert et al, 2000;Roegge et al, 2000;Widholm et al, 2001;Sugawara et al, 2006;Colciago et al, 2009), or phthalates (Zhao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Prenatal exposure to bisphenols and cognitive function in children at 7 years of age in the Swedish SELMA study

Cited by 36 publications

References 62 publications

Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

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