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Type: Journal article
Title: Reduction of mitochondrial function by FCCP during mouse cleavage stage embryo culture reduces birth weight and impairs the metabolic health of offspring
Author: Zander-Fox, D.
Fullston, T.
McPherson, N.
Sandeman, L.
Kang, W.
Good, S.
Spillane, M.
Lane, M.
Citation: Biology of Reproduction, 2015; 92(5):124-1-124-11
Publisher: Society for the Study of Reproduction
Issue Date: 2015
ISSN: 0006-3363
Statement of
Deirdre L. Zander-Fox, Tod Fullston, Nicole O. McPherson, Lauren Sandeman, Wan Xian Kang, Suzanne B. Good, Marni Spillane and Michelle Lane
Abstract: The peri-conceptual environment represents a critical window for programming fetal growth trajectories and susceptibility to disease however the underlying mechanism responsible for programming remains elusive. This study demonstrates a causal link between reduction of pre-compaction embryonic mitochondrial function and perturbed offspring growth trajectories and subsequent metabolic dysfunction. Incubation of embryos with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), which uncouples mitochondrial oxidative phosphorylation, significantly reduced mitochondrial membrane potential and ATP production in the 8-cell embryo and the number of inner cell mass cells within blastocysts however blastocyst development was unchanged. This perturbed embryo mitochondrial function was concomitant with reduced birth weight in female offspring following embryo transfer which persisted until weaning. FCCP treated females also exhibited increased adiposity at 4 weeks, increased adiposity gain between 4 weeks and 14 weeks, glucose intolerance at 8-weeks and insulin resistance at 14 weeks. Although FCCP treated males also exhibited reduced glucose tolerance their insulin sensitivity and adiposity gain between 4 to 14 weeks was unchanged. This is one of the first studies to demonstrate that reducing mitochondrial function and thus decreasing ATP output in the pre compacting embryo can influence offspring phenotype. This is of great significance as a large proportion of patients requiring assisted reproductive technologies are of advance maternal age or of a high body mass index which have both been independently linked with perturbed early embryonic mitochondrial function.
Keywords: blastocyst; developmental origins of health and disease; embryo; embryo culture; fetal development; mitochondria; pregnancy; preimplantation embryo
Description: Published online before print February 25, 2015
Rights: © 2015 by the Society for the Study of Reproduction, Inc.
RMID: 0030027781
DOI: 10.1095/biolreprod.114.123489
Appears in Collections:Paediatrics publications

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