Maternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children

Blaauwendraad, Sophia M; Gaillard, Romy; Santos, Susana; Sol, Chalana M.; Kannan, Kurunthachalam; Trasande, Leonardo; Jaddoe, Vincent W. V.

doi:10.1289/ehp10293

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…CVDs remain the leading cause of death and disability globally, and the risk factor characterization including environmental pollution deserved an urgent investigation . As one of the most widely used chemical compounds in daily consumer products, synthetic bisphenols have traditionally been recognized as an environmental health risk factor mainly as typical EDCs with steroid hormonal effects. − Epidemiological and animal data support the potential involvement of bisphenol exposure as for disrupting arterial health and developing CVD risk in humans. , Recent research suggested that the maternal bisphenol exposure level might influence fetal vascular development . Although these studies revealed the association between bisphenol exposure and CVDs, direct evidence and the underlying mechanism have not been delineated.…”

Section: Discussionmentioning

confidence: 99%

“…5,39 Recent research suggested that the maternal bisphenol exposure level might influence fetal vascular development. 40 Although these studies revealed the association between bisphenol exposure and CVDs, direct evidence and the underlying mechanism have not been delineated. Here, with multiple lines of evidence and cross-examination data, we demonstrate that bisphenols selectively interact with nuclear receptors to interfere with PI3K pathways and induce abnormal angiogenesis involved in the cardiovascular system.…”

Section: Discussionmentioning

confidence: 99%

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Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect

Shen

Cui

et al. 2023

Environ. Sci. Technol.

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Increased epidemiological evidence indicates the association of bisphenol exposure with human vascular disorders, while the underlying mechanism has not been clarified. Here, we sought to unveil the potential angiogenic effect and the underlying mechanism of bisphenols with different structural features using endothelial cells treated with an environmentally relevant concentration of bisphenols (range: 1 nM to 10 μM) and a C57BL/6 mouse model fed with doses of 0.002, 0.02, 2, and 20 mg/kg BW/day for 5 weeks. Bisphenol A (BPA) and bisphenol S (BPS) at a 1 nM level significantly increased tube formation by 45.1 and 30.2% and induced the microvessel sprouting, while tube length and microvessel sprouting were significantly inhibited by 37.2 and 55.7% after exposure to tetrabromobisphenol S (TBBPS) at 1 μM, respectively. Mechanistically, TBBPA and TBBPS significantly inhibited the interaction between phosphatidylinositol 3kinase (PI3K) and thyroid receptor (TR), while BPA and BPS favored the interaction between PI3K and estrogen receptor (ER), resulting in abnormal PI3K signaling with consequent distinct angiogenic activity. BPA-and BPS-induced pro-angiogenic effects and TBBPS showed anti-angiogenic effects due to their distinct disruption on the TR/ER-PI3K pathway. Our work provided new evidence and mechanistic insight on the angiogenic activity of bisphenols and expanded the scope of endocrine disruptors with interference in vascular homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect

Shen

Cui

et al. 2023

Environ. Sci. Technol.

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“…Therefore, the primary intake of bisphenols in humans is likely to occur through the diet, mainly through the consumption of canned foods or drinking bottled water ( Eladak et al, 2015 ). All this ultimately suggests a limitation of their use, also in consideration of the wide spectrum of comorbidities being associated to BPA usage ( Ma et al, 2019 ; Barra et al, 2022 ), even through the maternal route ( Blaauwendraad et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome profiling reveals several LncRNAs differentially expressed in idiopathic germ cell aplasia

Lavorgna

Tascini

Bertini

et al. 2022

Front. Cell Dev. Biol.

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Mechanisms underlying severe male infertility are still largely elusive. However, recently, a single-cell transcription study by our group identified several differentially expressed coding genes in all the somatic cell types in testes of patients with idiopathic germ cell aplasia (iGCA). Here, we leverage this work by extending the analysis also to the non-coding portion of the genome. As a result, we found that 43 LncRNAs were differentially expressed in the somatic cells of these patients. Interestingly, a significant portion of the overexpressed LncRNAs was found to be a target of TAF9B, a transcription factor known to be involved in germ cell survival. Moreover, several overexpressed LncRNAs were also found to be activated in a mouse model of Sertoli cells treated with bisphenol A, a widespread environmental contaminant, long suspected to impair male fertility. Finally, a literature search for MEG3, a maternally imprinted LncRNA overexpressed as well in our patients, found it to be involved, among other things, in obesity and inflammation, known comorbidities of iGCA, ultimately suggesting that our findings deepen the understanding of the molecular insights coupled not only to the pathogenesis, but also to the clinical course of this class of patients.

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“…For instance, a link between exposure to di(2ethylhexyl)-phthalate (DEHP) and a higher risk of CHD was observed in the Taiwanese population, 16 while a cohort study indicated that there was no association between maternal exposure to PAEs and carotid intima-media thickness (CIMT) in children. 17 A recent cross-sectional study reported a link between total concentrations of six common metabolites of PAHs in urine and the development of CHD and other cardiovascular diseases in the United States general population. 13 However, there is scarce evidence supporting this association, and the mechanisms through which PAH metabolites are connected to CHD have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Mediating Role of Glucose-Lipid Metabolism in the Association between the Increased Risk of Coronary Heart Disease and Exposure to Organophosphate Esters, Phthalates, and Polycyclic Aromatic Hydrocarbons

Zhang,

Liu,

et al. 2024

Environ. Health

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There is a lack of human evidence concerning the cardiovascular effects of combined exposure to endocrine disruptors. This case-control study sought to investigate coronary heart disease (CHD) associations with exposure to organophosphate flame retardants (OFRs), phthalates (PAEs), and polycyclic aromatic hydrocarbons (PAHs) among 148 adults with coronary-angiography-diagnosed CHD and 320 healthy adults from southern China. The mediating role of glucose-lipid metabolism was also explored. Bayesian kernel machine regression suggested that when exposure status was fixed to the 75th percentile with the median value as the reference, exposure to OFRs, PAEs, and PAHs was associated with an 84% (95% CI: 36%−134%), 132% (12%−252%), and 214% (89%−331%) increased risk of developing CHD, respectively. Weighted quantile sum regression indicated urinary bis(2-butoxyethyl) phosphate (BBOEP), dibutyl phosphate (DBP), monoisononyl phthalate (miNP), and metabolites of phenanthrene may be major contributors to the overall effect of mixtures. In further analyses on identified chemical risk factors, mediation analyses suggested exposure to phenanthrene may increase the risk of CHD via elevating total cholesterol and blood glucose, while exposure to DiNP mainly associates with serum lipids. Besides, we observed a slight mediation effect of oxidative DNA damage between urinary BBOEP and risk of CHD. These results provide potential direction for further experimental studies. Longitudinal evidence is needed to clarify the causation of the results.

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Maternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children

Cited by 15 publications

References 56 publications

Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect

Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect

Single-cell transcriptome profiling reveals several LncRNAs differentially expressed in idiopathic germ cell aplasia

Mediating Role of Glucose-Lipid Metabolism in the Association between the Increased Risk of Coronary Heart Disease and Exposure to Organophosphate Esters, Phthalates, and Polycyclic Aromatic Hydrocarbons

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