Trps1 regulates mouse zygotic genome activation and preimplantation embryo development via the PDE4D/AKT/CREB signaling pathway

  • Cell Biol Toxicol. 2025 Feb 20;41(1):48. doi: 10.1007/s10565-025-09999-1.
Xia Jiang  #  1 Weiwei Xu  #  1 Jiandong Sun  #  1  2  3  4 Jianmin Lin  1 Zihang Lin  1 Xiuli Lian  1  2 Shumin Liao  1 Shanshan Luo  1 Yue Liu  5  6 Shie Wang  7  8
Affiliations
  • 1. Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, 350122, People's Republic of China.
  • 2. Department of Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, People's Republic of China.
  • 3. Department of Andrology, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350122, People's Republic of China.
  • 4. Department of Reproductive Medicine Centre, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350122, People's Republic of China.
  • 5. Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, 350122, People's Republic of China. [email protected].
  • 6. Department of Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, People's Republic of China. [email protected].
  • 7. Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, 350122, People's Republic of China. [email protected].
  • 8. Department of Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, People's Republic of China. [email protected].
  • # Contributed equally.
Abstract

Despite zygotic genome activation (ZGA) is crucial for early embryonic development, its regulatory mechanism is still unclear in mammals. In the present study, we demonstrate that TRPS1, a maternal factor, plays an essential role in mouse early embryogenesis by regulating the transition from 2-cell to 4-cell embryos during preimplantation development. The absence of Trps1 could leads to impaired ZGA through Akt/CREB signaling pathway. Furthermore, our findings suggest that TRPS1 may modulate the transcription of Pde4d to influence Akt and CREB phosphorylation. Interestingly, compared to Trps1 knockdown alone, co-injection of Trps1 siRNA and Pde4d mRNA significantly enhances the development rate of 4-cell embryos. Collectively, these results indicate a negative involvement of Trps1 in mouse preimplantation embryo development by targeting the PDE4D/Akt/CREB pathway to regulate ZGA.

Keywords
AKT/CREB pathway; Phosphodiesterase 4d; Tricho-rhino-phalangeal syndrome 1; Zygotic genome activation.
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