Tuesday, 14 October 2014

Mitochondrial Fission Factor Drp1 Maintains Oocyte Quality via Dynamic Rearrangement of Multiple Organelles


Drp1 was knocked out in a transgenic line of female mice which were actively growing oocytes, to examine the effects mitochondrial dynamics on the development and aging of oocytes.

Effects on oocyte formation and growth
The Drp1 KO female mice produced less pups per mating (only 0.63 compared to the 6.7 pups per mating of control mice) despite normal vaginal plug formation. Few or no oocytes could be recovered from the KO mice, they therefore do not ovulate normally Follicle growth was low in KO ovaries and granulosa proliferation was blocked. Defects accumulated with age.

Effects on mitochondrial and ER morphology
Not surprisingly, Drp1 KO in oocytes lead to elongated and aggregated mitochondria. mtDNA nucleoids were clustered.  Most of the ER clustered around mitochondrial clusters. In control mice around 80% of the mitochondria were in contact with the ER, but in KO mice mitochondria tended to cluster with various other membranous structures (e.g. small vesicles). Peroxisomes and secretory vesicles were deformed.

Effects on energetics
There was no difference in membrane potential measured in mitochondria from control and KO oocytes and ATP content was not significantly affected.

Effects on calcium response
There were less calcium oscillations recorded in KO oocytes. The frequency of the oscillations was similar but the amplitude was reduced in KO mice.

Other observations
Oocytes contain a structure called the germinal vesicle, which is a nuclear structure and it is enlarged during oocyte maturation. The germinal vesicle breaks down before polar body formation. In normal mice, mitochondria move from the germinal vesicle to the cytoplasm during breakdown but this does not happen in KO mice. Mitochondrial movement is restricted in KO oocytes and the breakdown of the germinal vesicle is defective.   

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