Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009–2017

Frederiksen, Hanne; Nielsen, O.B.; Koch, Holger M.; Skakkebæk, Niels E.; Juul, Anders; Jørgensen, Niels; Andersson, Anna‐Maria

doi:10.1016/j.ijheh.2019.10.002

Cited by 134 publications

(95 citation statements)

References 65 publications

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“…Humans are widely exposed to bisphenol A (BPA), a highproduction-volume chemical (1), and bisphenol A diglycidyl ether (BADGE), both widely used in the production of, e.g., epoxy resins and food container linings (2). Due to concerns of the safety of BPA, it is increasingly substituted with analogous chemicals (3,4). Although evidence suggests that BPA and its analogs can interfere with human male fertility (4)(5)(6)(7)(8), the effects directly on human sperm function are less well-studied.…”

Section: Introductionmentioning

confidence: 99%

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

2020

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Aim: Evidence suggests that bisphenol A diglycidyl ether (BADGE), bisphenol A (BPA), and BPA analogs can interfere with human male fertility. However, the effect directly on human sperm function is not known. The CatSper Ca 2+ channel in human sperm controls important sperm functions and is necessary for normal male fertility. Environmental chemicals have been shown to activate CatSper and thereby affect Ca 2+ signaling in human sperm. BPA has previously been investigated for effects on Ca 2+ signaling human sperm, whereas the effects of other BPA analogs are currently unknown. The aim of this study is thus to characterize the effect of BADGE, BPA, and the eight analogs BPG, BPAF, BPC, BPB, BPBP, BPE, BPF, BPS on Ca 2+ signaling, and CatSper in human sperm. Methods: Direct effects of the bisphenols on Ca 2+ signaling in human sperm cells were evaluated using a Ca 2+ fluorimetric assay measuring changes in intracellular Ca 2+. Effects via CatSper were assessed using the specific CatSper inhibitor RU1968. Effects on human sperm function was assessed using an image cytometry-based acrosome reaction assay and the modified Kremer's sperm-mucus penetration assay. Results: At 10 µM the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP induced Ca 2+ signals in human sperm cells, whereas BPE, BPF, BPS, and BPA had no effect. The efficacy of the chemicals at 10 µM is BPG > BPAF > BPC > BADGE > BPB > BPBP. Dose-response relations of BPG, BPAF, BPC, BADGE, BPB, and BPBP yielded EC50-values in the nM-µM range. The induced Ca 2+ signals were almost completely abolished using the CatSper inhibitor RU1968, indicating an effect of the bisphenols on CatSper. All bisphenols, except BPBP, were found to dose-dependently inhibit progesterone-induced Ca 2+ signals, with BPG and BPAF displaying inhibition even in low µM doses. BPG and BPAF were shown to affect human sperm function in a progesterone-like manner. Rehfeld et al. Bisphenols Activate Human CatSper Conclusion: Our results show that the bisphenols BPG, BPAF, BPC, BADGE, BPB, and BPBP can affect Ca 2+ signaling in human sperm cells through activation of CatSper. This could potentially disrupt human sperm function by interfering with normal CatSpersignaling and thus be a contributing factor in human infertility, either alone or in mixtures with other chemicals.

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Section: Introductionmentioning

confidence: 99%

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

2020

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“…Unfortunately, despite preventable air pollution, the use of certain pesticides that have been banned for many years still persist in the soil and continue to pose a threat to public health. This is the case everywhere, even if some studies tend to show a decreased level of exposure in the last decade; for instance, in Denmark [576]. In some areas of the world, pollution-related brain disorders can be even further increased by malnutrition since several studies show that diabetes alters the BBB permeability [577].…”

Section: Discussionmentioning

confidence: 99%

Brain Disorders and Chemical Pollutants: A Gap Junction Link?

et al. 2020

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The incidence of brain pathologies has increased during last decades. Better diagnosis (autism spectrum disorders) and longer life expectancy (Parkinson’s disease, Alzheimer’s disease) partly explain this increase, while emerging data suggest pollutant exposures as a possible but still underestimated cause of major brain disorders. Taking into account that the brain parenchyma is rich in gap junctions and that most pollutants inhibit their function; brain disorders might be the consequence of gap-junctional alterations due to long-term exposures to pollutants. In this article, this hypothesis is addressed through three complementary aspects: (1) the gap-junctional organization and connexin expression in brain parenchyma and their function; (2) the effect of major pollutants (pesticides, bisphenol A, phthalates, heavy metals, airborne particles, etc.) on gap-junctional and connexin functions; (3) a description of the major brain disorders categorized as neurodevelopmental (autism spectrum disorders, attention deficit hyperactivity disorders, epilepsy), neurobehavioral (migraines, major depressive disorders), neurodegenerative (Parkinson’s and Alzheimer’s diseases) and cancers (glioma), in which both connexin dysfunction and pollutant involvement have been described. Based on these different aspects, the possible involvement of pollutant-inhibited gap junctions in brain disorders is discussed for prenatal and postnatal exposures.

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“…Currently, its content in sunscreen products must not exceed 6%, and in other cosmetics, its content can reach up to 0.5% (Commission Regulation 2017/238). However, benzophenone-3 is still widely used as a UV filter in many other consumer products and in other noncosmetic industries, which potentially explains why, despite the restrictions, the benzophenone-3 content measured in urine samples from different populations is still not reduced (Frederiksen et al, 2020).…”

Section: Exposure Routes Of the Human Body To Benzophenone-3mentioning

confidence: 99%

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Wnuk

Kajta

2021

Acta Biochim Pol

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Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, oxybenzone, or BP-3) is one of the most frequently used UV radiation absorbents, which are commonly referred to as sunscreen filters. Its widespread use in industrial applications provides protection against the photodegradation of a wide range of products but at the same time creates the risk of human exposure to benzophenone-3 unbeknownst to the individuals exposed. Topically applied benzophenone-3 penetrates individual skin layers, enters the bloodstream, and is excreted in the urine. In addition, benzophenone-3 easily crosses the placental barrier, which creates the risk of exposure to this substance in the prenatal period. Despite the widespread use and occurrence of benzophenone-3 in the human environment, little knowledge of the mechanisms underlying the effect of benzophenone-3 on the nervous system was available until recently. Only the most recent research, including studies by our group, has enabled the identification of new molecular mechanisms through which benzophenone-3 affects embryonic neuronal cells and the developing mammalian brain. Benzophenone-3 has been shown to induce neurotoxicity and apoptotic processes and inhibit autophagy in embryonic neuronal cells. Benzophenone-3 also alters expression and impairs function of receptors necessary for the proper development and function of the nervous system. The most worrying finding seems to be that benzophenone-3 contributes to an increased risk of developmental abnormalities and/or epigenetically based degeneration of neuronal cells by changing the epigenetic status of neuronal cells.

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Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009–2017

Cited by 134 publications

References 65 publications

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol Analogs, but Not Bisphenol A (BPA), Activate the CatSper Ca2+ Channel in Human Sperm

Brain Disorders and Chemical Pollutants: A Gap Junction Link?

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

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