Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis.

Abstract

To examine whether mtDNA is uni-or biparentally transmitted in mice, we developed an assay that can detect sperm mtDNA in a single mouse embryo. In

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

“…Several of these genes are involved in the internal apoptotic pathway and have interaction with mitochondria which having a critical role in this pathway. MtDNA is inherited from the mother's ovum [15], and it is unusual for sperm cells to contribute to mitochondria when fertilizing the oocyte. Mature oocytes have at least 100,000 copy of mtDNA [16].…”

Hybrid male sterility is caused by mitochondrial DNA deletion

“…Sperm mtDNA elimination by the egg is a system with high species specificity [10]. It is considered that this system evolved in order to eliminate parasites imported along with the sperm [11] and sperm mtDNA damaged by reactive oxygen species (ROS) [12].…”

The sperm mitochondria-specific translocator has a key role in maternal mitochondrial inheritance

“…To satisfy our hypothesis, which states that the sperm factor of sperm mitochondria selectively 28 incorporates the elimination factor in the fertilized egg, sperm mitochondria must retain protein-translocation functions after fertilization. Based on the findings that sperm mtDNA is not eliminated in interspecific crosses, is detected in the neonate (Kaneda et al, 1995) and partially survives if sperm mitochondria are transplanted into mtDNA-free Rho0 cells (Manfredi et al, 1997), we assumed that spermatozoa mitochondria retain normal functions. Furthermore, our Western blotting assay showed that Tom40 undergoes post-translational modification in the spermatozoa, suggesting that the Tom complex is a necessary apparatus in sperm mitochondria; it would therefore maintain its function as a protein translocator.…”

“…This suggests that a sperm mitochondria-specific substance might 4 be incorporated into the sperm mitochondria during spermatogenesis. Moreover, the mtDNA of sperm from mice with a heterogeneous mitochondrial and nuclear genome was not eliminated, whereas that from mice in which only the mitochondrial genome was heterogeneous was destroyed (Kaneda et al, 1995). This indicates that the sperm mitochondria-specific substance might be a protein encoded not by the mitochondrial genome but by the nuclear genome.…”

“…Kaneda et al, (1995) showed that sperm mitochondrial DNA (mtDNA) is lost by the late pronucleus stage immediately after incorporation, using intraspecific crosses of congenic mice that incorporated heterogeneous mtDNA (for detection by PCR). Observation of sperm mitochondria using rhodamine123-generated fluorescence, which is dependent upon the mitochondrial membrane action potential, showed the loss of fluorescence up to the late pronucleus stage (Kaneda et al, 1995). The microinjection of spermatid and liver cell mitochondria into eggs resulted in only the spermatid mitochondria being eliminated (Shitara et al, 2000).…”