Transient stress and stress enzyme responses have practical impacts on parameters of embryo development, from IVF to directed differentiation of stem cells

Abstract

In this review, we discuss the expression, regulation, downstream mechanisms, and function of stress-induced stress enzymes in mammalian oocytes, peri-implantation embryos, and the stem cells derived from those embryos. Recent reports suggest that stress enzymes mediate developmental functions during early mammalian development, in addition to the homeostatic functions shared with somatic cells. Stress-induced enzymes appear to insure that necessary developmental events occur: many of these events may occur at a slower rate, although some may occur more rapidly. Developmental events induced by stress may be mediated by a single dominant enzyme, but there are examples of responses that require the integration of more than one stress enzyme. The discussion focuses on the consequences of stress as a function of duration and magnitude, and this includes an emerging understanding of the threshold levels of duration and magnitude that lead to pathology. Other topics discussed are the reversibility of the developmental as well as homeostatic consequences of stress, the further problems with readaptation after stress subsides, and the mechanisms and functions of stress enzymes during early mammalian development. The analyses are done with specific concern for their practical impact in assisted reproductive technology (ART) and stem cell technologies.

Stress-Induced Enzyme Activation Primes Murine Embryonic Stem Cells to Differentiate Toward the First Extraembryonic Lineage

“…Previous work in our lab established 400 mM sorbitol as the dose that induced the highest levels of stress enzyme activity and function in mouse TSCs and embryos [41,46,47]. Our mESC studies therefore began with this dose, but it proved to be lethal in mESCs (Fig.…”

Female Tract Cytokines and Developmental Programming in Embryos

“…The rates of cell division, differentiation and/or cell death that accompany progression from zygote to blastocyst are highly sensitive to disruption by various environmental stressors, some of which alter growth factor balance and bioavailability (Xie et al 2008). Most notably, culture ex vivo exerts cell stress resulting in fewer blastomeres, due both to retarded progression through the cell cycle and elevated incidence of apoptosis (Xie et al 2006).…”

Stress responses at the endometrial–placental interface regulate labyrinthine placental differentiation from trophoblast stem cells

“…2; Zhong et al 2007, 2010, Xie et al 2008, 2010, Liu et al 2009. The stress enzymes our laboratory has studied most are stressactivated protein kinase protein (aka MAPK8/9, SAPK/ JNK1/2) and AMPK (aka AMPKa1/2, PRKAA1/2).…”