Mitochondrial Mutations In Primate Oocytes

One of the most promising leads related to mitochondrial mutations in primate oocytes has been found in the control region of the mitochondrial genome. The main control region of mtDNA, or the D-loop, is adjacent to transcription promoters, is the most variable portion of the human mitochondrial genome, may contain hetero-plasmic point mutations, and is responsible for DNA replication. Our laboratory showed that an oocyte-specific mtDNA point mutation occurs frequently in oocytes of some women (Barritt et al., 2000; Michikawa et al., 1999) and appeared to be more prevalent in the oocytes of women of advanced reproductive age. This point mutation represents a single base pair transversion of a thymine (T) to guanine (G) at base pair 414 (T414G) in the mitochondrial genome. DNA sequence analysis confirmed this mutation in only one oocyte from 11 patients aged 26 to 36 (n = 23), compared to 17 oocytes from 10 patients aged 37 to 42 (n = 43). The younger group exhibited this mtDNA point mutation in only 4% of oocytes compared to 40% from the older group (p < 0.01). Therefore, single human oocytes may contain the mtDNA T414G transversion point mutation, which accumulates with age. The potential significance of this point mutation may be its correlation with reproductive senescence or ovarian reserve. Furthermore, other oocyte-specific mutations may also be present in the mitochon-drial control region and thus may be responsible for impaired transcription and replication regulation. If these potentially high copy number point mutations can be confirmed by more extensive studies in normal oocytes from aging primates, this could be an important and unrecognized factor in pregnancy outcome because mitochondrial replication is believed not to begin until after implantation. Therefore, replication defects would not be expected to compromise preimplantation development, but depending upon mutant load, could manifest as postimplantation death. These data imply that ES cell lines derived from embryos made with oocytes from older individuals (human or monkey) may exhibit impaired mitochondrial function.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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