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Type: Journal article
Title: Disruption of Mitochondrial Malate-Aspartate Shuttle Activity in Mouse Blastocysts Impairs Viability and Fetal Growth
Author: Mitchell, M.
Cashman, K.
Gardner, D.
Thompson, J.
Lane, M.
Citation: Biology of Reproduction, 2009; 80(2):295-301
Publisher: Soc Study Reproduction
Issue Date: 2009
ISSN: 0006-3363
Statement of
Megan Mitchell, Kara S. Cashman, David K. Gardner, Jeremy G. Thompson and Michelle Lane
Abstract: Dietary supply of nutrients, both periconception and during pregnancy, influence the growth and development of the fetus and offspring and their health into adult life. Despite the importance of research efforts surrounding the developmental origins of health and disease hypothesis, the biological mechanisms involved remain elusive. Mitochondria are of major importance in the oocyte and early embryo, particularly as a source of ATP generation, and perturbations in their function have been related to reduced embryo quality. The present study examined embryo development following periconception exposure of females to a high-protein diet (HPD) or a low-protein diet (LPD) relative to a medium-protein diet (MPD; control), and we hypothesized that perturbed mitochondrial metabolism in the mouse embryo may be responsible for the impaired embryo and fetal development reported by others. Although the rate of development to the blastocyst stage did not differ between diets, both the HPD and LPD reduced the number of inner cell mass cells in the blastocyst-stage embryo. Furthermore, mitochondrial membrane potential was reduced and mitochondrial calcium levels increased in the 2-cell embryo. Embryos from HPD females had elevated levels of reactive oxygen species and ADP concentrations, indicative of metabolic stress and, potentially, the uncoupling of oxidative phosphorylation, whereas embryos from LPD females had reduced mitochondrial clustering around the nucleus, suggestive of an overall quietening of metabolism. Thus, although periconception dietary supply of different levels of protein is permissive of development, mitochondrial metabolism is altered in the early embryo, and the nature of the perturbation differs between HPD and LPD exposure.
Keywords: Cells, Cultured; Mitochondria; Blastocyst; Animals; Mice, Inbred C57BL; Mice, Inbred CBA; Mice; Aminooxyacetic Acid; Malates; Malate Dehydrogenase; Aspartate Aminotransferase, Cytoplasmic; Aspartic Acid; Enzyme Inhibitors; Biological Transport; Fetal Development; Fetal Viability; Pregnancy; Female
Description: Copyright © 2009 by the Biology of Reproduction
RMID: 0020090083
DOI: 10.1095/biolreprod.108.069864
Appears in Collections:Obstetrics and Gynaecology publications

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