Document Detail

Impaired Mitochondrial Function in the Preimplantation Embryo Perturbs Fetal and Placental Development in the Mouse.
MedLine Citation:
PMID:  21076083     Owner:  NLM     Status:  Publisher    
The preimplantation embryo is sensitive to its environment and despite having some plasticity to adapt, perturbing environments can impair embryo development, metabolic homeostasis, fetal and placental development, and offspring health. This study used an in vitro model of embryo culture with increasing mitochondrial inhibition to directly establish the effect of impaired mitochondrial function on embryo, fetal and placental development. Culture in the absence of the carbohydrate pyruvate (-P) significantly increased blastocyst glucose oxidation via glycolysis to maintain normal levels of ATP and TCA cycle activity. This resulted in a significant reduction in blastocyst development, trophectoderm cell number and respiration rate, but importantly did not impair implantation rates or fetal and placental development. In contrast, increasing concentrations of the mitochondrial inhibitor, Amino-oxyacetate (AOA) impaired glycolysis, TCA cycle activity, respiration rate and ATP production, incrementally reduced blastocyst development, and decreased blastocyst inner cell mass and trophectoderm cell numbers. Importantly, AOA did not affect implantation rates, however, 5 µM AOA significantly reduced placental growth but not fetal growth, increasing fetal: placental weight ratio. Furthermore, 50 µM AOA significantly reduced both placental and fetal growth but not fetal: placental weight ratio. Hence this study demonstrates a threshold of mitochondrial function is required for normal development and despite developmental plasticity of the embryo, impaired mitochondrial function in the embryo affects subsequent fetal and placental growth. These results highlight the importance of mitochondrial function in regulating pre- and post-implantation development, however, the effect on offspring health remains unknown.
Sarah L Wakefield; Michelle Lane; Megan Mitchell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-11-10
Journal Detail:
Title:  Biology of reproduction     Volume:  -     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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