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 Esr1 gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of Esr2, Gper1, Ahr, Arnt, Cyp19a1, Cyp1a1, and Atg7, 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.
Highlights
Introduction iationsTriclocarban (3,4,40 -trichlorocarbanilide, TCC) is a broad-spectrum antimicrobial agent that is added to a wide variety of personal and health care products, medical devices, plastics, and fabrics [1]
We aimed to explore the mechanisms through which prenatal exposure to triclocarban affects postnatal mice of both sexes, with a particular emphasis on apoptosis, autophagy, steroid/xenobioticreceptor-related expression, and epigenetic modifications that occur in response to triclocarban
In one-month-old male mice, prenatal exposure to triclocarban resulted in a significant decrease in the level of Esr1 mRNA (Figure 1A)
Summary
Introduction iationsTriclocarban (3,4,40 -trichlorocarbanilide, TCC) is a broad-spectrum antimicrobial agent that is added to a wide variety of personal and health care products, medical devices, plastics, and fabrics [1]. Excessive use of compounds with antibacterial potential has resulted in antimicrobial resistance, which contributes to 700,000 deaths annually [2]. It is known that fetuses are susceptible to the potential effects of triclocarban since this compound possesses high placental transferability and lower excretion capacity from fetal bodies [3]. Research conducted over the past 6 years shows that triclocarban has a strong influence on embryonic and fetal development. Kennedy et al [4] provided evidence that exposure to triclocarban during lactation influences the development of neonates and affects neonatal rat survival. Another in vivo study based on maternal exposure of mouse offspring through breastfeeding showed that triclocarban accumulates
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