Figure 5.

Regulation and the impact of ER stress/UPR signaling cascades during oogenesis and preimplantation. During folliculogenesis, enhanced IRE1α, PERK, GRP78 and XPB1s levels in the granulosa cells of large secondary follicles and later stages as well as elevated XBP1s levels in cumulus cells from fertilized oocytes indicate physiological involvement of UPR signaling during oogenesis and fertilization. However, increased fatty acid levels and obesity can dysregulate protein secretion and mitochondrial activity by impairing ER homeostasis, causing abnormal embryonic development. Salubrinal treatment of cumulus-oocyte complex maintains normal preimplantation embryo development by reversing these conditions. The preimplantation embryo also requires extensive protein synthesis for proper development and implantation. Severe ER stress induced by tunicamycin in 2-cell stage embryos does not affect development until the end of morula stage. However, severe ER stress impairs blastocyst formation via extensive apoptosis. Use of TUDCA completely reverses these negative effects, indicating that ER homeostasis is crucial during blastocyst formation and subsequent development.