OBJECTIVE: The age-associated changes of mtDNA include nucleotide deletion, point mutations, as well as modifications. Age associated alterations of mtDNA occur in several different species; however, their physiological relevance remains unclear. The function of human ovary changes dramatically around the menopausal period. However, the mechanism of menopause and ovarian aging is not well understood. Thus, to study the regulatory mechanism of ovarian dysfunction by aging, the accumulation of mtDNA deletions in human ovaries from pre-menopausal and menopausal women was analyzed and compared with mtDNA deletions in myoma and myometriums of the same subjects. METHOD: Total DNA was extracted from these tissues, an part of mtDNA were amplified by polymerase chain reaction. The detailed locations of each of the deleted mtDNA regions were identified by sequencing. RESULT: Four types of mtDNA deletions were identified: a 4977 bp deletion, a 3805 bp deletion, a 7150 bp deletion, and a 5777 bp deletion. In ovaries, the occurrence of a 4977 bp deletion of mtDNA in menopausal women was significantly higher than that in pre-menopausal women, i.e., 62.5% of that in menopausal women and 20.0% of that in pre-menopausal women. In menopausal women, the occurrence of all of those four mtDNA deletions identified in this study in ovaries was higher than that in myomas and myometriums. CONCLUSION: A 4977 bp deletion of mtDNA between the ATPase 8 and ND5 genes in ovaries can be related to ovarian aging, especially during menopause. A 4977 bp deletion in ovaries of menopausal women can be a usuful marker of natural ovarian aging and may have a relationship to dysfunction of the ovarian aging. Three other mtDNA deletions identified in this study, a 3809 bp deletion, 7150 bp deletion, and 5777 bp deletion, was newly reported. A 5777bp deletion was found in a large amount in Korean women and further studies about this racial specificity will be needed.
Adenosine Triphosphatases ; Aging ; Animals ; DNA ; DNA, Mitochondrial* ; Female ; Humans* ; Menopause ; Mice ; Myoma ; Myometrium ; Ovary* ; Point Mutation ; Polymerase Chain Reaction ; Sensitivity and Specificity