Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR) in Mammalian Oocyte Maturation and Preimplantation Embryo Development

Abstract

Mammalian oocytes and early embryos derived from in vitro production are highly susceptible to a variety of cellular stresses. During oocyte maturation and preimplantation embryo development, functional proteins must be folded properly in the endoplasmic reticulum (ER) to maintain oocyte and embryo development. However, some adverse factors negatively impact ER functions and protein synthesis, resulting in the activation of ER stress and unfolded protein response (UPR) signaling pathways. ER stress and UPR signaling have been identified in mammalian oocytes and embryos produced in vitro, suggesting that modulation of ER stress and UPR signaling play very important roles in oocyte maturation and the development of preimplantation embryos. In this review, we briefly describe the current state of knowledge regarding ER stress, UPR signaling pathways, and their roles and mechanisms in mammalian (excluding human) oocyte maturation and preimplantation embryo development.

Oleic Acid Counters Impaired Blastocyst Development Induced by Palmitic Acid During Mouse Preimplantation Development: Understanding Obesity-Related Declines in Fertility

“…There are many more experimental designs and time course experiments that must be conducted to fully understand this outcome, and we are very interested in pursuing outcomes to those stage-specific effects in future experiments. Our results are consistent with the growing conclusion that OA is protective against PA’s effects, specifically in that it alleviates PA-induced ER stress in mouse preimplantation embryos [ 22 – 27 , 34 ].…”

“…Treatment of bovine COCs with FFAs impairs blastocyst development; however, rescue by the unfolded protein response (UPR)/endoplasmic reticulum (ER) stress pathway inhibitor salubrinal identified UPR activation as a major contributor to FFA-dependent developmental decreases [ 21 ]. Studies conducted over the past decade have indicated that the preimplantation embryo is armed with several key stress response mechanisms that, in part, offset the deleterious effects of stress on early development (for review see [ 22 , 23 ]). Most notably, these are the ER stress pathways, which oversee the unfolded protein response (UPR) and activate stress-responsive gene expression patterns in an attempt to allow the early embryo to effectively adapt to and survive both external and internal stressors [ 22 , 23 ].…”

“…Studies conducted over the past decade have indicated that the preimplantation embryo is armed with several key stress response mechanisms that, in part, offset the deleterious effects of stress on early development (for review see [ 22 , 23 ]). Most notably, these are the ER stress pathways, which oversee the unfolded protein response (UPR) and activate stress-responsive gene expression patterns in an attempt to allow the early embryo to effectively adapt to and survive both external and internal stressors [ 22 , 23 ]. Studies, including ours, have demonstrated the presence and action of ER stress pathways throughout preimplantation development [ 24 – 27 ].…”

Hyperthermia Disturbs and Delays Spontaneous Differentiation of Human Embryoid Bodies

“…In addition, the treatment of cells with the chemical chaperone TUDCA significantly reduced PERK signaling, which was increased in a short period of time under heat stress, and restored the levels of three-germ-layer-specific genes to normal. This finding is consistent with that of a previous study, which showed that relieving ER stress in mammalian cells in vitro had positive effects on embryo survival and development [26]. However, how TUDCA affects embryonic development and protects embryos from heat stress using an in vivo model should be explored in the future.…”

Knock out of Specific Maternal Vitellogenins in Zebrafish (Danio Rerio) Evokes Vital Changes in Egg Proteomic Profiles that resemble the Phenotype of Poor Quality Eggs

“…Accumulation of misfolded and/or unfolded proteins in the ER lumen disturbs its functioning, leading to ER stress. The ERQC (ER quality control system) is in charge of identifying properly folded proteins versus misfolded proteins [45,46]. Properly folded proteins which are approved by the ERQC are channeled for transport to the Golgi complex, while those misfolded proteins are retained in the ER to undergo correct folding or to be targeted for proteolysis by the ER degradation (ERAD) machinery [45,46].…”