Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain
Benzophenone-3 (BP-3), commonly used as a UV filter in personal care products and as a stabilizer, is an alleged endocrine disruptor with potential neurodevelopmental impacts. Despite its abundance in the environment, the studies on its effect on brain development are scarce, especially in terms of...
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MDPI AG
2024-12-01
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| author | Karolina Przepiórska-Drońska Andrzej Łach Bernadeta Angelika Pietrzak-Wawrzyńska Joanna Rzemieniec Małgorzata Kajta Agnieszka Wawrzczak-Bargieła Wiktor Bilecki Karolina Noworyta Agnieszka Wnuk |
| author_facet | Karolina Przepiórska-Drońska Andrzej Łach Bernadeta Angelika Pietrzak-Wawrzyńska Joanna Rzemieniec Małgorzata Kajta Agnieszka Wawrzczak-Bargieła Wiktor Bilecki Karolina Noworyta Agnieszka Wnuk |
| author_sort | Karolina Przepiórska-Drońska |
| collection | DOAJ |
| description | Benzophenone-3 (BP-3), commonly used as a UV filter in personal care products and as a stabilizer, is an alleged endocrine disruptor with potential neurodevelopmental impacts. Despite its abundance in the environment, the studies on its effect on brain development are scarce, especially in terms of multigenerational impact. In this work, for the first time, we examined neurotoxic and pro-apoptotic effects of BP-3 on mouse brain regions (cerebral cortex and hippocampus) in both the first (F<sub>1</sub>) and second (F<sub>2</sub>) generations after maternal exposure to environmentally relevant BP-3 levels. We found disregulated markers of cell damage (LDH, H<sub>2</sub>O<sub>2</sub>, caspase-3 and -8) and observed increased expression of pro-apoptotic <i>Fas</i>/FAS or <i>Fasl</i>/FASL. BP-3 exposure disrupted the BAX/BCL2 pathway, showing stronger effects in the F<sub>1</sub> than in the F<sub>2</sub> generation, with a dominance of extrinsic pathway (FAS, FASL, caspase-8) over intrinsic one (BAX, BCL2), suggesting that BP-3-induced apoptosis primarily operates via the extrinsic pathway and could impair brain homeostasis across generations. This study underscores the potential of BP-3 to increase multigenerational risks associated with disrupted neurodevelopment and highlights the importance of understanding its long-term neurotoxic effects. |
| format | Article |
| id | doaj-art-12cd53430b174c7aa5fc777331dd1e5d |
| institution | Kabale University |
| issn | 2305-6304 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj-art-12cd53430b174c7aa5fc777331dd1e5d2024-12-27T14:56:45ZengMDPI AGToxics2305-63042024-12-01121290610.3390/toxics12120906Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse BrainKarolina Przepiórska-Drońska0Andrzej Łach1Bernadeta Angelika Pietrzak-Wawrzyńska2Joanna Rzemieniec3Małgorzata Kajta4Agnieszka Wawrzczak-Bargieła5Wiktor Bilecki6Karolina Noworyta7Agnieszka Wnuk8Laboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, PolandDepartment of Pharmaceutical Sciences, University of Milan, 20133 Milan, ItalyLaboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, PolandDepartment of Pharmacology and Brain Biostructure, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandDepartment of Pharmacology and Brain Biostructure, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandAffective Cognitive Neuroscience Laboratory, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandLaboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, PolandBenzophenone-3 (BP-3), commonly used as a UV filter in personal care products and as a stabilizer, is an alleged endocrine disruptor with potential neurodevelopmental impacts. Despite its abundance in the environment, the studies on its effect on brain development are scarce, especially in terms of multigenerational impact. In this work, for the first time, we examined neurotoxic and pro-apoptotic effects of BP-3 on mouse brain regions (cerebral cortex and hippocampus) in both the first (F<sub>1</sub>) and second (F<sub>2</sub>) generations after maternal exposure to environmentally relevant BP-3 levels. We found disregulated markers of cell damage (LDH, H<sub>2</sub>O<sub>2</sub>, caspase-3 and -8) and observed increased expression of pro-apoptotic <i>Fas</i>/FAS or <i>Fasl</i>/FASL. BP-3 exposure disrupted the BAX/BCL2 pathway, showing stronger effects in the F<sub>1</sub> than in the F<sub>2</sub> generation, with a dominance of extrinsic pathway (FAS, FASL, caspase-8) over intrinsic one (BAX, BCL2), suggesting that BP-3-induced apoptosis primarily operates via the extrinsic pathway and could impair brain homeostasis across generations. This study underscores the potential of BP-3 to increase multigenerational risks associated with disrupted neurodevelopment and highlights the importance of understanding its long-term neurotoxic effects.https://www.mdpi.com/2305-6304/12/12/906apoptosisbenzophenone-3environmentally pervasive chemicalsmultigenerational changesneurotoxicityprenatal exposure |
| spellingShingle | Karolina Przepiórska-Drońska Andrzej Łach Bernadeta Angelika Pietrzak-Wawrzyńska Joanna Rzemieniec Małgorzata Kajta Agnieszka Wawrzczak-Bargieła Wiktor Bilecki Karolina Noworyta Agnieszka Wnuk Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain Toxics apoptosis benzophenone-3 environmentally pervasive chemicals multigenerational changes neurotoxicity prenatal exposure |
| title | Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain |
| title_full | Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain |
| title_fullStr | Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain |
| title_full_unstemmed | Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain |
| title_short | Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain |
| title_sort | multigenerational consequences of prenatal exposure to benzophenone 3 demonstrate sex and region dependent neurotoxic and pro apoptotic effects in mouse brain |
| topic | apoptosis benzophenone-3 environmentally pervasive chemicals multigenerational changes neurotoxicity prenatal exposure |
| url | https://www.mdpi.com/2305-6304/12/12/906 |
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