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Comment |
Repeated superovulation may affect mitochondrial functions of cumulus cells in mice. Xie JK et al. (2016) Controlled ovarian stimulation by exogenous gonadotrophins is a key procedure during the in vitro fertilization cycle to obtain a sufficient number of oocytes in humans. Previous studies demonstrated that repeated superovulation had deleterious effects on the ovaries. However, whether repeated superovulation adversely affects the mitochondrial functions of cumulus cells remains unclear. In this study, mice were divided into three groups: superovulation once (R1); superovulation three times (R3), and superovulation five times (R5). We evaluated the effects of repeated superovulation on mitochondrial DNA copies (mtDNA) and observed decreased mtDNA copies per cell with increasing number of superovulation cycles. Further, we investigated the DNA methylation status in exon 2 and the mRNA expression level of nuclear-encoded DNA polymerase gamma A (PolgA). The results showed that the DNA methylation levels of PolgA in R1 and R5 were slightly lower than in R3. Additionally, the altered DNA methylation in PolgA coincided with the changes in PolgA expression in cumulus cells. We also found that the mRNA expression of COX1, CYTB, ND2, and ND4 was altered by repeated superovulation in cumulus cells. Thus, repeated superovulation had adverse effects on mitochondrial function.//////////////////
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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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