Stress signaling in mammalian oocytes and embryos: a basis for intervention and improvement of outcomes

Abstract

Oocytes and early stage embryos are highly sensitive to variation in diverse exogenous factors such as temperature, osmolarity, oxygen, nutrient restriction, pH, shear stress, toxins, amino acid availability, and lipids. It is becoming increasingly apparent that many such factors negatively affect the endoplasmic reticulum, protein synthesis and protein processing, initiating ER stress and unfolded protein responses. As a result, ER stress signaling serves as a common mediator of cellular responses to diverse stressors. In oocytes and embryos, this leads to developmental arrest and epigenetic changes. Recent studies have revealed that preventing ER stress or inhibiting ER stress signaling can preserve or even enhance oocyte and embryo developmental potential. This review examines ER stress signaling, how it arises, how it affects oocytes and embryos, and how its occurrence can be managed or prevented.

Keywords: Autophagy; ER stress; Epigenetic; Preimplantation embryo; Unfolded protein response.

Figure 1

Three main branches of the ER stress response. Upon accumulation of unfolded protein within the ER, GRP78 (HSPA5) dissociates from PERK(EIF2AK3), ATF6 and IRE1(ERN1), to bind to the unfolded protein. These three effectors initiate early events that are pro-survival (green box). With prolonged or more severe ER stress, these effectors direct later events that lead to apoptosis (red box). Other events, such as caspase-12 activation contribute to apoptosis (not shown).

Figure 2

Relationship between stage of development, stressors, multiple stress response pathways, and developmental outcomes. Stressors can act upon oocytes, early embryos, or placenta. ER stress activation can accompany other stress responses. The cellular responses to ER stress can include apoptosis, autophagy, recovery, and epigenetic changes that can lead to developmental abnormalities.