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.