Permanent embryo arrest: molecular and cellular concepts

被引:111
作者
Betts, D. H. [1 ]
Madan, P. [1 ]
机构
[1] Univ Guelph, Ontario Vet Coll, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
anti-apoptosis; p66Shc; ROS; telomere; mitochondria;
D O I
10.1093/molehr/gan035
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Developmental arrest is one 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 H2O2 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.
引用
收藏
页码:445 / 453
页数:9
相关论文
共 152 条
[1]   Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress [J].
Ahmed, Shaheda ;
Passos, Joao F. ;
Birket, Matthew J. ;
Beckmann, Tina ;
Brings, Sebastian ;
Peters, Heiko ;
Birch-Machin, Mark A. ;
von Zglinicki, Thomas ;
Saretzki, Gabriele .
JOURNAL OF CELL SCIENCE, 2008, 121 (07) :1046-1053
[2]   TELOMERE SHORTENING IS ASSOCIATED WITH CELL-DIVISION IN-VITRO AND IN-VIVO [J].
ALLSOPP, RC ;
CHANG, E ;
KASHEFIAAZAM, M ;
ROGAEV, EI ;
PIATYSZEK, MA ;
SHAY, JW ;
HARLEY, CB .
EXPERIMENTAL CELL RESEARCH, 1995, 220 (01) :194-200
[3]   TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS [J].
ALLSOPP, RC ;
VAZIRI, H ;
PATTERSON, C ;
GOLDSTEIN, S ;
YOUNGLAI, EV ;
FUTCHER, AB ;
GREIDER, CW ;
HARLEY, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10114-10118
[4]   Cytogenetic analysis of human preimplantation embryos following developmental arrest in vitro [J].
Almeida, PA ;
Bolton, VN .
REPRODUCTION FERTILITY AND DEVELOPMENT, 1998, 10 (06) :505-513
[5]   Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE [J].
Andersen, A. Nyboe ;
Goossens, V. ;
Ferraretti, A. P. ;
Bhattacharya, S. ;
Felberbaum, R. ;
de Mouzon, J. ;
Nygren, K. G. .
HUMAN REPRODUCTION, 2008, 23 (04) :756-771
[6]   GENE ACTIVITY AND CLEAVAGE ARREST IN HUMAN PREEMBRYOS [J].
ARTLEY, JK ;
BRAUDE, PR ;
JOHNSON, MH .
HUMAN REPRODUCTION, 1992, 7 (07) :1014-1021
[7]   Is telomere length one of the determinants of reproductive life span? [J].
Aydos S.E. ;
Elhan A.H. ;
Tükün A. .
Archives of Gynecology and Obstetrics, 2005, 272 (2) :113-116
[8]   Telomere instability in the male germline [J].
Baird, DM ;
Britt-Compton, B ;
Rowson, J ;
Amso, NN ;
Gregory, L ;
Kipling, D .
HUMAN MOLECULAR GENETICS, 2006, 15 (01) :45-51
[9]   Effects of ambient oxygen concentration on the growth and antioxidant defenses of human cell cultures established from fetal and postnatal skin [J].
Balin, AK ;
Pratt, L ;
Allen, RG .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (03) :257-267
[10]   DNA damage signalling guards against activated oncogenes and tumour progression [J].
Bartek, J. ;
Bartkova, J. ;
Lukas, J. .
ONCOGENE, 2007, 26 (56) :7773-7779