PMID- 34884933
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20220107
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 23
DP  - 2021 Dec 4
TI  - 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.
LID - 10.3390/ijms222313121 [doi]
LID - 13121
AB  - 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.
FAU - Wnuk, Agnieszka
AU  - Wnuk A
AUID- ORCID: 0000-0003-3620-3902
AD  - Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj 
      Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 
      Krakow, Poland.
FAU - Rzemieniec, Joanna
AU  - Rzemieniec J
AUID- ORCID: 0000-0002-5732-2794
AD  - Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj 
      Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 
      Krakow, Poland.
FAU - Przepiorska, Karolina
AU  - Przepiorska K
AD  - Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj 
      Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 
      Krakow, Poland.
FAU - Pietrzak, Bernadeta Angelika
AU  - Pietrzak BA
AD  - Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj 
      Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 
      Krakow, Poland.
FAU - Mackowiak, Marzena
AU  - Mackowiak M
AUID- ORCID: 0000-0002-6056-9595
AD  - Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, 
      Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 
      31-343 Krakow, Poland.
FAU - Kajta, Malgorzata
AU  - Kajta M
AD  - Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj 
      Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 
      Krakow, Poland.
LA  - eng
GR  - 2015/19/B/NZ7/02449/National Science Center/
GR  - N/A/the statutory fund of the Maj Institute of Pharmacology at the Polish Academy 
      of Sciences in Krakow, Poland/
PT  - Journal Article
DEP - 20211204
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Infective Agents, Local)
RN  - 0 (Carbanilides)
RN  - 0 (Esr1 protein, mouse)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Neurotransmitter Agents)
RN  - BGG1Y1ED0Y (triclocarban)
SB  - IM
MH  - Animals
MH  - Anti-Infective Agents, Local/toxicity
MH  - Blood-Brain Barrier/drug effects
MH  - Brain/*drug effects
MH  - Carbanilides/*toxicity
MH  - DNA Methylation/drug effects
MH  - Epigenesis, Genetic/drug effects
MH  - Estrogen Receptor alpha/*metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Mice
MH  - Neurogenesis/*drug effects/genetics
MH  - Neurotransmitter Agents/genetics/metabolism
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Sex Factors
MH  - Signal Transduction/drug effects
PMC - PMC8658534
OTO - NOTNLM
OT  - DNA methylation
OT  - environmentally pervasive chemicals
OT  - estrogen receptors
OT  - microarrays
OT  - xenobiotic receptors
COIS- The authors declare that they have no actual or potential conflicts of interest, 
      including any financial, personal, or other relationships that could 
      inappropriately influence or be perceived to influence the submitted work.
EDAT- 2021/12/11 06:00
MHDA- 2022/01/08 06:00
PMCR- 2021/12/04
CRDT- 2021/12/10 01:05
PHST- 2021/10/19 00:00 [received]
PHST- 2021/11/30 00:00 [revised]
PHST- 2021/12/01 00:00 [accepted]
PHST- 2021/12/10 01:05 [entrez]
PHST- 2021/12/11 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/12/04 00:00 [pmc-release]
AID - ijms222313121 [pii]
AID - ijms-22-13121 [pii]
AID - 10.3390/ijms222313121 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Dec 4;22(23):13121. doi: 10.3390/ijms222313121.