PMID- 37278767
OWN - NLM
STAT- MEDLINE
DCOM- 20230707
LR  - 20231010
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 97
IP  - 8
DP  - 2023 Aug
TI  - The mechanisms governing mouse embryonic palate mesenchymal cells' proliferation 
      associated with atRA-induced cleft palate in mice: insights from integrated 
      transcriptomic and metabolomic analyses.
PG  - 2143-2153
LID - 10.1007/s00204-023-03534-z [doi]
AB  - While exposure to high levels of all-trans retinoic acid (atRA) during pregnancy 
      is known to suppress murine embryonic palate mesenchymal (MEPM) cells 
      proliferation and to result in cleft palate (CP) development, the underlying 
      mechanisms are poorly understood. Accordingly, this study was designed with the 
      goal of clarifying the etiological basis for atRA-induced CP. A murine model of 
      CP was established via the oral administration of atRA to pregnant mice on 
      gestational day (GD) 10.5, after which transcriptomic and metabolomic analyses 
      were performed with the goal of clarifying the critical genes and metabolites 
      associated with CP development through an integrated multi-omics approach. MEPM 
      cells proliferation was altered by atRA exposure as expected, contributing to CP 
      incidence. In total, 110 genes were differentially expressed in the atRA 
      treatment groups, suggesting that atRA may influence key biological processes 
      including stimulus, adhesion, and signaling-related activities. In addition, 133 
      differentially abundant metabolites were identified including molecules 
      associated with ABC transporters, protein digestion and absorption, mTOR 
      signaling pathway, and the TCA cycle, suggesting a link between these mechanisms 
      and CP. Overall, combined analyses of these transcriptomic and metabolomic 
      results suggested that the MAPK, calcium, PI3K-Akt, Wnt, and mTOR signaling 
      pathways are particularly important pathways enriched in the palatal cleft under 
      conditions of atRA exposure. Together, these integrated transcriptomic and 
      metabolomic approaches provided new evidence with respect to the mechanisms 
      underlying altered MEPM cells proliferation and signal transduction associated 
      with atRA-induced CP, revealing a possible link between oxidative stress and 
      these pathological changes.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Yu, Zengli
AU  - Yu Z
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
AD  - College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
FAU - Song, Shuaixing
AU  - Song S
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
AD  - College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
FAU - Wang, Guoxu
AU  - Wang G
AD  - College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
FAU - Zhang, Yujing
AU  - Zhang Y
AD  - College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
FAU - Zhang, Yaxin
AU  - Zhang Y
AD  - College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
FAU - Wu, Yang
AU  - Wu Y
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
FAU - Liu, Hongyan
AU  - Liu H
AD  - Department of Medical Genetics, Henan Provincial People's Hospital, Zhengzhou, 
      450003, China.
FAU - Zhang, Yuwei
AU  - Zhang Y
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
FAU - Liu, Xiaozhuan
AU  - Liu X
AUID- ORCID: 0000-0002-8956-4341
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, 450003, China. 
      754245185@qq.com.
LA  - eng
GR  - No. 81801547/The Natural Science Foundation of China/
GR  - No. SBGJ202102014/Key project of science, technology of Henan province/
GR  - No. 222102310418/Key project of science, technology of Henan province/
GR  - No.18XTZX12009/Major Projects of Collaborative Innovation of Zhengzhou/
GR  - No. 201300310800/Hubei Technological Innovation Special Fund/
PT  - Journal Article
DEP - 20230606
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Animals
MH  - Mice
MH  - *Cleft Palate/chemically induced/genetics/pathology
MH  - Transcriptome
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Tretinoin/toxicity
MH  - Cell Proliferation
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - All-trans retinoic acid
OT  - Cleft palate
OT  - Integrated multi-omics study
OT  - Metabolomics
OT  - Transcriptomics
EDAT- 2023/06/06 13:09
MHDA- 2023/07/07 06:42
CRDT- 2023/06/06 11:05
PHST- 2023/04/21 00:00 [received]
PHST- 2023/05/24 00:00 [accepted]
PHST- 2023/07/07 06:42 [medline]
PHST- 2023/06/06 13:09 [pubmed]
PHST- 2023/06/06 11:05 [entrez]
AID - 10.1007/s00204-023-03534-z [pii]
AID - 10.1007/s00204-023-03534-z [doi]
PST - ppublish
SO  - Arch Toxicol. 2023 Aug;97(8):2143-2153. doi: 10.1007/s00204-023-03534-z. Epub 
      2023 Jun 6.