Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways As Well As Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Dec 10

PMID 34884933

Citations 4

Authors

Agnieszka Wnuk

Joanna Rzemieniec

Karolina Przepiorska

Bernadeta Angelika Pietrzak

Marzena Mackowiak

Malgorzata Kajta

Affiliations

Soon will be listed here.

Abstract

Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of , , , , , , and , and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes.

Citing Articles

Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain.

Przepiorska-Dronska K, Lach A, Pietrzak-Wawrzynska B, Rzemieniec J, Kajta M, Wawrzczak-Bargiela A Toxics. 2025; 12(12.

PMID: 39771121 PMC: 11728767. DOI: 10.3390/toxics12120906.

Selective Activation of G Protein-Coupled Estrogen Receptor 1 (GPER1) Reduces ER Stress and Pyroptosis via AMPK Signaling Pathway in Experimental Subarachnoid Hemorrhage.

Liang Y, Fu W, Tang Y, Ye H, Wang Y, Sun C Mol Neurobiol. 2024; 62(1):871-884.

PMID: 38935231 DOI: 10.1007/s12035-024-04312-3.

Posttreatment with PaPE-1 Protects from Aβ-Induced Neurodegeneration Through Inhibiting the Expression of Alzheimer's Disease-Related Genes and Apoptosis Process That Involves Enhanced DNA Methylation of Specific Genes.

Pietrzak-Wawrzynska B, Wnuk A, Przepiorska-Dronska K, Lach A, Kajta M Mol Neurobiol. 2023; 61(7):4130-4145.

PMID: 38064105 PMC: 11236864. DOI: 10.1007/s12035-023-03819-5.

Hypermethylation of the ADIRF promoter regulates its expression level and is involved in NNK-induced malignant transformation of lung bronchial epithelial cells.

Xiong R, Du Y, Chen S, Liu T, Ding X, Zhou J Arch Toxicol. 2023; 97(12):3243-3258.

PMID: 37777989 DOI: 10.1007/s00204-023-03608-y.

Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies.

Wnuk A, Przepiorska K, Pietrzak B, Kajta M Int J Mol Sci. 2023; 24(4).

PMID: 36835454 PMC: 9968034. DOI: 10.3390/ijms24044043.

References

Liu M, Xie W, Zheng W, Yin D, Luo R, Guo F . [Targeted binding of estradiol with ESR1 promotes proliferation of human chondrocytes by inhibiting activation of ERK signaling pathway]. Nan Fang Yi Ke Da Xue Xue Bao. 2019; 39(2):134-143. PMC: 6765635. DOI: 10.12122/j.issn.1673-4254.2019.09.02. View

Kajta M, Rzemieniec J, Wnuk A, Lason W . Triclocarban impairs autophagy in neuronal cells and disrupts estrogen receptor signaling via hypermethylation of specific genes. Sci Total Environ. 2019; 701:134818. DOI: 10.1016/j.scitotenv.2019.134818. View

Iacopetta D, Catalano A, Ceramella J, Saturnino C, Salvagno L, Ielo I . The Different Facets of Triclocarban: A Review. Molecules. 2021; 26(9). PMC: 8126057. DOI: 10.3390/molecules26092811. View

Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H . g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res. 2019; 47(W1):W191-W198. PMC: 6602461. DOI: 10.1093/nar/gkz369. View

Fleming A, Rubinsztein D . Autophagy in Neuronal Development and Plasticity. Trends Neurosci. 2020; 43(10):767-779. DOI: 10.1016/j.tins.2020.07.003. View

Nakagawa S, Deli M, Kawaguchi H, Shimizudani T, Shimono T, Kittel A . A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int. 2008; 54(3-4):253-63. DOI: 10.1016/j.neuint.2008.12.002. View

Ge S, Jung D, Yao R . ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics. 2019; 36(8):2628-2629. PMC: 7178415. DOI: 10.1093/bioinformatics/btz931. View

Wnuk A, Rzemieniec J, Lason W, Krzeptowski W, Kajta M . Apoptosis Induced by the UV Filter Benzophenone-3 in Mouse Neuronal Cells Is Mediated via Attenuation of Erα/Pparγ and Stimulation of Erβ/Gpr30 Signaling. Mol Neurobiol. 2017; 55(3):2362-2383. PMC: 5840254. DOI: 10.1007/s12035-017-0480-z. View

La Barbera L, Vedele F, Nobili A, DAmelio M, Krashia P . Neurodevelopmental Disorders: Functional Role of Ambra1 in Autism and Schizophrenia. Mol Neurobiol. 2019; 56(10):6716-6724. DOI: 10.1007/s12035-019-1557-7. View

10.

Wnuk A, Rzemieniec J, Litwa E, Lason W, Kajta M . Prenatal exposure to benzophenone-3 (BP-3) induces apoptosis, disrupts estrogen receptor expression and alters the epigenetic status of mouse neurons. J Steroid Biochem Mol Biol. 2018; 182:106-118. DOI: 10.1016/j.jsbmb.2018.04.016. View

11.

Dong N, Zhu J, Han W, Wang S, Yan Z, Ma D . Maternal methamphetamine exposure causes cognitive impairment and alteration of neurodevelopment-related genes in adult offspring mice. Neuropharmacology. 2018; 140:25-34. DOI: 10.1016/j.neuropharm.2018.07.024. View

12.

Hess J, Radonjic N, Patak J, Glatt S, Faraone S . Autophagy, apoptosis, and neurodevelopmental genes might underlie selective brain region vulnerability in attention-deficit/hyperactivity disorder. Mol Psychiatry. 2020; 26(11):6643-6654. PMC: 8760041. DOI: 10.1038/s41380-020-00974-2. View

13.

Chung E, Genco M, Megrelis L, Ruderman J . Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos. Proc Natl Acad Sci U S A. 2011; 108(43):17732-7. PMC: 3203771. DOI: 10.1073/pnas.1115187108. View

14.

Aref-Eshghi E, Kerkhof J, Pedro V, Barat-Houari M, Ruiz-Pallares N, Andrau J . Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders. Am J Hum Genet. 2020; 106(3):356-370. PMC: 7058829. DOI: 10.1016/j.ajhg.2020.01.019. View

15.

Tarnow P, Tralau T, Hunecke D, Luch A . Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells. Toxicol In Vitro. 2013; 27(5):1467-75. DOI: 10.1016/j.tiv.2013.03.003. View

16.

Rzemieniec J, Bratek E, Wnuk A, Przepiorska K, Salinska E, Kajta M . Neuroprotective effect of 3,3'-Diindolylmethane against perinatal asphyxia involves inhibition of the AhR and NMDA signaling and hypermethylation of specific genes. Apoptosis. 2020; 25(9-10):747-762. PMC: 7527327. DOI: 10.1007/s10495-020-01631-3. View

17.

Aker A, McConnell R, Loch-Caruso R, Park S, Mukherjee B, Rosario Z . Interactions between chemicals and non-chemical stressors: The modifying effect of life events on the association between triclocarban, phenols and parabens with gestational length in a Puerto Rican cohort. Sci Total Environ. 2019; 708:134719. PMC: 6957748. DOI: 10.1016/j.scitotenv.2019.134719. View

18.

Li Z, Ueki K, Kumagai K, Araki R, Otsuki Y . Regulation of bcl-2 transcription by estrogen receptor-α and c-Jun in human endometrium. Med Mol Morphol. 2013; 47(1):43-53. DOI: 10.1007/s00795-013-0043-y. View

19.

Eads C, Danenberg K, Kawakami K, Saltz L, Blake C, Shibata D . MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 2000; 28(8):E32. PMC: 102836. DOI: 10.1093/nar/28.8.e32. View

20.

Xie F, Xiao P, Chen D, Xu L, Zhang B . miRDeepFinder: a miRNA analysis tool for deep sequencing of plant small RNAs. Plant Mol Biol. 2012; . DOI: 10.1007/s11103-012-9885-2. View