PMID- 36369707
OWN - NLM
STAT- MEDLINE
DCOM- 20230206
LR  - 20230224
IS  - 2472-1727 (Electronic)
VI  - 115
IP  - 3
DP  - 2023 Feb 1
TI  - Gestational exposure to triphenyl phosphate induces epigenetic modifications in 
      C57Bl/6 fetal liver.
PG  - 338-347
LID - 10.1002/bdr2.2121 [doi]
AB  - INTRODUCTION: Triphenyl phosphate (TPHP) is a chemical flame retardant and 
      plasticizer which is added to consumer and industrial products. The developmental 
      origins of health and disease hypothesis postulate that in utero exposures can 
      have later-in-life effects on the developing fetus and can alter fetal gene 
      expression. This study aimed to determine whether epigenetic modifications 
      occurred following in utero TPHP exposure in mice and whether these changes were 
      dose and/or sex-dependent. METHODS: Pregnant C57Bl/6 mice were treated with 0, 5, 
      25, or 50 mg/kg of TPHP on gestational days (GD) 8, 10, 12, and 14 via 
      intraperitoneal injection and fetal livers were collected on GD 19. Changes in 
      the levels of acetylation of H3 and H4, as well as methylation of H3K9 and global 
      DNA methylation were assessed in the fetal livers by western blot. RESULTS: 
      Results showed that there was a significant decrease in fetal DNA methylation 
      following in utero exposure to 50 mg/kg TPHP compared to the control (0 mg/kg) 
      independent of the sex of the fetus. While there were no significant alterations 
      compared to controls in any histone modifications at any dose or sex following in 
      utero TPHP exposure, we did note a decrease (t test, p = .025) in the levels of 
      acetylated H3 in males versus females following a maternal dose of 25 mg/kg. The 
      monomethylated H3K9 levels were also increased in females versus males following 
      exposure to TPHP at 5 mg/kg (p = .018) and 25 mg/kg (p = .027) when analyzed via 
      unpaired t tests, although not significantly different from controls. DISCUSSION: 
      The results suggest that gestational TPHP exposure can induce epigenetic 
      modifications in murine fetal tissue. Specifically, global DNA methylation levels 
      were downregulated in response to TPHP. Additionally, males appear to be more 
      sensitive to TPHP-induced histone modifications than females. These data support 
      the need for further studies investigating the impacts of gestational TPHP 
      exposure on the developing fetus.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Shafique, Sidra
AU  - Shafique S
AUID- ORCID: 0000-0001-9200-3652
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada.
FAU - Wolpert, Sydney H
AU  - Wolpert SH
AD  - School of Environmental Studies, Queen's University, Kingston, Ontario, Canada.
FAU - Philbrook, Nicola A
AU  - Philbrook NA
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada.
FAU - Winn, Louise M
AU  - Winn LM
AUID- ORCID: 0000-0003-1088-5538
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada.
AD  - School of Environmental Studies, Queen's University, Kingston, Ontario, Canada.
LA  - eng
GR  - RGPIN-2019-05638/National Sciences and Engineering Research Council of Canada/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221111
PL  - United States
TA  - Birth Defects Res
JT  - Birth defects research
JID - 101701004
RN  - YZE19Z66EA (triphenyl phosphate)
RN  - 0 (Organophosphates)
SB  - IM
MH  - Pregnancy
MH  - Male
MH  - Female
MH  - Animals
MH  - Mice
MH  - *Epigenesis, Genetic
MH  - *DNA Methylation
MH  - Organophosphates/toxicity
MH  - Mice, Inbred C57BL
MH  - Liver
OTO - NOTNLM
OT  - DNA methylation
OT  - acetylated H3
OT  - fetal liver
OT  - histone modifications
OT  - monomethylated H3K9
OT  - triphenyl phosphate
EDAT- 2022/11/13 06:00
MHDA- 2023/02/07 06:00
CRDT- 2022/11/12 01:12
PHST- 2022/09/26 00:00 [revised]
PHST- 2022/05/14 00:00 [received]
PHST- 2022/10/18 00:00 [accepted]
PHST- 2022/11/13 06:00 [pubmed]
PHST- 2023/02/07 06:00 [medline]
PHST- 2022/11/12 01:12 [entrez]
AID - 10.1002/bdr2.2121 [doi]
PST - ppublish
SO  - Birth Defects Res. 2023 Feb 1;115(3):338-347. doi: 10.1002/bdr2.2121. Epub 2022 
      Nov 11.