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Comment |
Decreased expression of mitochondrial genes in human unfertilized oocytes and arrested embryos. Hsieh RH et al. (2004) To evaluate the relationship between mitochondrial gene expression of oocytes/embryos and their fertilizability in unfertilized oocytes, arrested embryos, and tripronucleate zygotes, because both nuclear and cytoplasmic factors contribute to oocyte activation, fertilization, and subsequent development. Prospective laboratory research. In vitro fertilization (IVF) laboratory in a university hospital. Seventy-five unfertilized oocytes, 45 arrested embryos, and 24 tripronucleate (3PN) embryos from 45 female patients undergoing IVF. Analysis of mitochondrial gene expression by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Comparison of the expression levels of mitochondrial genes including ND2, CO I, CO II, ATPase 6, CO III, ND3, ND6, and Cyt b in three groups. Significantly decreased transcription levels were expressed in unfertilized oocytes and arrested embryos. The average expression levels of the eight determined genes compared with the control (GAPDH) was 4.4 +/- 0.7, 6.4 +/- 1.1, and 13.2 +/- 1.1 in unfertilized oocytes, arrested embryos, and 3PN embryos, respectively. Significantly decreased expressions of the ATPase 6, CO III, and ND3 genes were detected from samples with 4977-bp common deletion in the mitochondrial DNA (mtDNA) compared with the non-deletion group. The present study is the first report to present globally decreased mitochondrial gene expression levels in human compromised oocytes and embryos. These data support the notion that the down-regulation of mitochondrial RNA by defective oxidative phosphorylation genes possibly affects oocyte quality including fertilization and further embryo development.//////////////////
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Mutations |
1 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: SSR 2010 abstract 114. Mitochondrial DNA Mutations in Reproductive Medicine. Weiwei
Fan and Douglas C. Wallace. Salk Institute for Biological Studies, La Jolla, CA,
USA; University of California, Irvine, CA, USA
We have created the first mouse model of directional segregation of a
heteroplasmic mtDNA frameshift mutation during oogenesis. The same mice also
developed maternally inherited mitochondrial cardiomyopathy caused by a
homoplasmic mtDNA missense mutation. A mouse cell line was first isolated
containing a homoplasmic COI T6589C missense mutation and a homoplasmic ND6
13885insC frameshift mutation. The mutant mtDNA was next introduced into the
female mouse embryonic stem (mES) cells. One of the resulting mES cybrids
contained both homoplasmic mutations but 4% of its mtDNAs acquired a T deletion
adjacent to the ND6 13885insC (ND6 13885insCdelT), which restored the normal
ND6 coding sequence. After transmitted into the mouse germline, the COI T6589C
mutation remained homoplasmic but the ND6 frameshift mutation dropped to 47% in
the founder mouse and to 14% to 6% to 0% in the successive generations. The
resulting homoplasmic COI T6589C + ND6 13885insCdelT mutant mice had a 37%-
48% complex IV deficiency in brain, heart, liver, and skeletal muscle and increased
heart mitochondrial proliferation, disordered mitochondrial distribution, and cristaelysis.
Echo cardiograms revealed that these animals developed a hypertrophic
cardiomyopathy associated with a 26% increase in left ventricular wall thickness, a
30% decrease in left ventricular diastolic internal dimension, a 39% decrease in
circumferential strain, and a 74% decrease in radial strain. This stable maternally
inherited mouse model now opens new avenues for studying the pathophysiology and
therapeutic of mitochondrial diseases.
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