Permanent embryo arrest: molecular and cellular concepts.
Developmental arrest is one of the mechanisms responsible for the elevated levels of embryo demise during the first week of in vitro development. Approximately 10-15% of IVF embryos permanently arrest in mitosis at the 2- to 4-cell cleavage stage showing no indication of apoptosis. Reactive oxygen species (ROS) are implicated in this process and must be controlled in order to optimize embryo production. A stress sensor that can provide a key understanding of permanent cell cycle arrest and link ROS with cellular signaling pathway(s) is p66Shc, an adaptor protein for apoptotic-response to oxidative stress. Deletion of the p66Shc gene in mice results in extended lifespan, which is linked to their enhanced resistance to oxidative stress and reduced levels of apoptosis. p66Shc has been shown to generate mitochondrial H(2)O(2) to trigger apoptosis, but may also serve as an integration point for many signaling pathways that affect mitochondrial function. We have detected elevated levels of p66Shc and ROS within arrested embryos and believe that p66Shc plays a central role in regulating permanent embryo arrest. In this paper, we review the cellular and molecular aspects of permanent embryo arrest and speculate on the mechanism(s) and etiology of this method of embryo demise.
Betts
D H
DH
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1. bettsd@uoguelph.ca
Madan
P
P
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D017382:Reactive Oxygen Species; D055765:Shc Signaling Adaptor Proteins