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  3. MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway

MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway

  • Theriogenology. 2024 May 24:225:152-161. doi: 10.1016/j.theriogenology.2024.05.037.
Xiu-Li Zhang 1,  Zhi-Yong An 2,  Gao-Jie Lu 3,  Tuo Zhang 4,  Cheng-Wei Liu 5,  Meng-Qi Liu 6,  Qing-Xin Wei 7,  Lin-Hu Quan 8,  Jin-Dan Kang 9
Affiliations

Affiliations

  • 1 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 1612308913@qq.com.
  • 2 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 56245398@qq.com.
  • 3 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: lgj1904406294@163.com.
  • 4 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 2911713681@qq.com.
  • 5 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: muyuanlcw@163.com.
  • 6 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 1274835015@qq.com.
  • 7 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 2483566243@qq.com.
  • 8 College of Pharmacy, Yanbian University, Yanji, 133002, China. Electronic address: lhquan@ybu.edu.cn.
  • 9 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanji, 133002, China. Electronic address: jdkang@ybu.edu.cn.
PMID: 38805997 DOI: 10.1016/j.theriogenology.2024.05.037
Abstract

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of Reactive Oxygen Species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and Beclin1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced Apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the Monocarboxylate Transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased Apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.

Keywords

AMPK; Early embryo development; MCT1; Porcine; Valeric acid.

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