Telomeres and aging-related meiotic dysfunction in women.
Meiotic dysfunction increasingly afflicts women as they age, resulting in infertility, miscarriage and handicapped offspring. How aging disrupts meiotic function in women remains unclear, but as women increasingly delay childbearing, this issue becomes urgent. Telomeres, which mediate aging in mitotic cells, may also mediate aging during meiosis. Telomeres shorten during DNA replication. In mammals, oocytes remain quiescent, but their precursors replicated during fetal oogenesis. Moreover, eggs ovulated from older women entered meiosis later during fetal oogenesis than eggs ovulated when younger, and therefore underwent more replications. Telomeres also shorten from reactive oxygen, which triggers a DNA repair response, so the prolonged interval between fetal oogenesis and ovulation in some women would further shorten telomeres. Mice normally do not exhibit age-related meiotic dysfunction (interestingly, their telomeres are manyfold longer than telomeres in women), but genetic or pharmacologic shortening of mouse telomeres recapitulates the reproductive aging phenotype of women. This has led to a telomere theory of age-related meiotic dysfunction in women, and underlined the importance to human health of a mechanistic understanding of telomeres and meiosis.
Keefe
D L
DL
Department of Ob/Gyn, University of South Florida, Harbourside Medical Tower, Tampa, FL 33606, USA. dkeefe@hsc.usf.edu
Liu
L
L
Marquard
K
K
D000818:Animals; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D005260:Female; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D009630:Nondisjunction, Genetic / Q000235:genetics*; D012098:Reproduction / Q000235:genetics* / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000502:physiology*