Acute exposure to triphenyl phosphate inhibits the proliferation and cardiac differentiation of mouse embryonic stem cells and zebrafish embryos

Zenghua Qi, Min Chen, Yuanyuan Song, Xiya Wang, Bingkun Li, Zhi Feng Chen, Suk Ying Tsang*, Zongwei CAI

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Attention has recently paid to the interaction of triphenyl phosphate (TPHP) and body tissues, particularly within the reproductive and development systems, due to its endocrine-disrupting properties. However, the acute effects of TPHP on early embryonic development remain unclear. Here, we used mouse embryonic stem cells (mESC) and zebrafish embryos to investigate whether TPHP is an embryo toxicant. First, we found that continuous exposure of TPHP decreased the proliferation and increased the apoptotic populations of mESCs in a concentration-dependent manner. Results of mass spectrometry showed that the intracellular concentration of TPHP reached 39.45 ± 7.72 µg/g w/w after 3 hr of acute exposure with TPHP (38.35 μM) but gradually decreased from 3 hr to 48 hr. Additionally, DNA damage was detected in mESCs after a short-term treatment with TPHP, which in turn, activated DNA damage responses, leading to cell cycle arrest by changing the expression levels of p53, proliferating cell nuclear antigen, and Y15-phosphorylated Cdk I. Furthermore, our results revealed that short-term treatment with TPHP disturbed cardiac differentiation by decreasing the expression levels of Oct4, Sox2, and Nanog and transiently reduced the glycolysis capacity in mESCs. In zebrafish embryos, exposure to TPHP resulted in broad, concentration-dependent developmental defects and coupled with heart malformation and reduced heart rate. In conclusion, the two models demonstrate that acute exposure to TPHP affects early embryonic development and disturbs the cardiomyogenic differentiation.

Original languageEnglish
Pages (from-to)21235-21248
Number of pages14
JournalJournal of Cellular Physiology
Volume234
Issue number11
DOIs
Publication statusPublished - Nov 2019

Scopus Subject Areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

User-Defined Keywords

  • cardiac differentiation
  • developmental and reproduction toxicity
  • mouse embryonic stem cells
  • proliferation
  • Triphenyl phosphate

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