J Vet Sci.  2017 Mar;18(1):1-9. 10.4142/jvs.2017.18.1.1.

Reactive oxygen species-mediated unfolded protein response pathways in preimplantation embryos

• Ali I
• Shah SZ
• Jin Y
• Li ZS
• Ullah O
• Fang NZ

• KMID: 2412581
• DOI: http://doi.org/10.4142/jvs.2017.18.1.1

Abstract

Excessive production of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress-mediated responses are critical to embryonic development in the challenging in vitro environment. ROS production increases during early embryonic development with the increase in protein requirements for cell survival and growth. The ER is a multifunctional cellular organelle responsible for protein folding, modification, and cellular homeostasis. ER stress is activated by a variety of factors including ROS. Such stress leads to activation of the adaptive unfolded protein response (UPR), which restores homeostasis. However, chronic stress can exceed the toleration level of the ER, resulting in cellular apoptosis. In this review, we briefly describe the generation and impact of ROS in preimplantation embryo development, the ROS-mediated activation mechanism of the UPR via the ER, and the subsequent activation of signaling pathways following ER stress in preimplantation embryos.

Keyword

blastocyst; endoplasmic reticulum; reactive oxygen species; unfolded protein response

MeSH Terms

Animals
Blastocyst/*metabolism
*Embryonic Development
Endoplasmic Reticulum/physiology
*Endoplasmic Reticulum Stress
Mammals/*embryology
Reactive Oxygen Species/*metabolism
Signal Transduction
*Unfolded Protein Response
Reactive Oxygen Species

Figure

• 

  Fig. 1 Schematic diagram of in vitro developing cells exposed to an increased ROS level, inducing hypoxia and activating endoplasmic reticulum (ER) stress. During ER stress, immunoglobulin-binding protein (BiP) binds to misfolded proteins and ultimately activates three branches of the unfolded protein response (UPR): (1) protein kinase-like ER kinase (PERK); (2) inositol-requiring enzyme 1 alpha (IRE1α); and (3) activating transcription factor 6 (ATF6). PERK is activated by dimerization and autophosphorylation, leading to phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), which activates transcription of ATF4, inducing the transcription of downstream genes. IRE1α produces a spliced form of Xbp1 due to its RNase activity. ATF6 is translocated from the ER to the Golgi body and is cleaved by protease activity to form active nuclear ATF6.

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