2. Academic Validation
  3. Peroxisome proliferator-activated receptor gamma (PPARγ) promotes the morula-to-blastocyst transition in Tibetan sheep embryos by enhancing mitophagy through suppression of the AKT/mTOR pathway

Peroxisome proliferator-activated receptor gamma (PPARγ) promotes the morula-to-blastocyst transition in Tibetan sheep embryos by enhancing mitophagy through suppression of the AKT/mTOR pathway

  • Int J Biol Macromol. 2025 Oct 17;331(Pt 2):148371. doi: 10.1016/j.ijbiomac.2025.148371.
Tianhao Li 1,  Yangyang Pan 1,  Tian Zhao 2,  Xuefeng Bai 1,  Donglan Zhong 1,  Yuejiao Liao 1,  Qiyong Zuo 1,  Xin Liu 1,  Sijiu Yu 3,  Yan Cui 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine of Gansu Agricultural University, Lanzhou, 730070, China; Gansu Livestock Embryo Engineering Technology Innovation Center, Lanzhou, 730070, China.
  • 2 College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, 066600, China.
  • 3 College of Veterinary Medicine of Gansu Agricultural University, Lanzhou, 730070, China; Gansu Livestock Embryo Engineering Technology Innovation Center, Lanzhou, 730070, China. Electronic address: [email protected].
  • 4 College of Veterinary Medicine of Gansu Agricultural University, Lanzhou, 730070, China; Gansu Livestock Embryo Engineering Technology Innovation Center, Lanzhou, 730070, China. Electronic address: [email protected].
PMID: 41110574 DOI: 10.1016/j.ijbiomac.2025.148371
Abstract

The morula-to-blastocyst transition (MBT) is a critical stage for successful embryo implantation, yet it represents the main developmental block during in vitro culture. In this study, transcriptomic and proteomic analyses were used to investigate the molecular mechanisms underlying MBT in Tibetan sheep embryos. The results revealed that oxidative stress and Mitophagy levels were significantly elevated during MBT, with PPAR-γ identified as a key regulatory factor. Pharmacological inhibition of PPAR-γ expression was performed, and changes in the expression of downstream factors (PPAR-γ, p-PPAR-γ, Akt, p-AKT, mTOR, p-mTOR, PINK1, PARKIN, and LC3), as well as ROS levels and mitochondrial membrane potential, were assessed using RT-qPCR and immunofluorescence. The findings showed that inhibition of PPAR-γ activated the Akt/mTOR signaling pathway, decreased the expression of PINK1, PARKIN, and LC3, and reduced ROS accumulation. These results demonstrated that PPAR-γ negatively regulates the Akt/mTOR pathway while being positively correlated with blastocyst development. In conclusion, PPAR-γ promotes MBT by enhancing mitochondrial quality control and maintaining redox and energy homeostasis.

Keywords

Early embryonic development; Mitophagy; Morula-to-blastocyst transition; PPAR-γ/AKT/mTOR; Tibetan sheep.

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