Telomeres and meiosis in health and disease

Abstract

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.

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

“…The shortened telomere length observed in the leukocytes of both male and female partners of couples experiencing iRPL is the first such study, though shorter telomere have been reported only in female partner experiencing recurrent miscarriages [16]. It is well known that telomere is a marker for cellular aging because their length declines with each cell division, though it exhibits inter-individual variation [31].…”

“…It is known that telomere DNA shortening is associated with genomic instability and may play a role in development of aneuploidy commonly found in female germ cells and human embryos [42]. Telomere length has been both positively and negatively associated with different measures of reproductive aging and contradictory results are reported [16,43,44]. Telomere shortening, therefore, could explain many of the manifestations of reproductive senescence.…”

“…From these observations it is suspected that telomeres might play an important role in chromosomal localization within the sperm nucleus [14], where abnormal chromosome localization leads to meiotic errors which results in sperm borne aneuploidies [15]. Moreover telomere length in human unfertilized oocytes has been correlated with the morphological appearance of embryo and embryo quality in sibling fertilized oocytes as well as the probability of pregnancy [10,16], surprisingly, there are few reports showing association of telomere length with various reproductive disorders. Hence this study was planned with the aim to assess the role of telomere length in the leukocytes of couples (both male and female partner) experiencing iRPL.…”

Organismal stress, telomeres and life histories

“…A minimum number of repeats is necessary for proper folding to occur. In addition to protecting the chromosome ends, telomeres also appear to be involved in regulating chromosome segregation during both mitosis and meiosis (Aubert and Lansdorp, 2008;Keefe, 2007).…”

The Long and Short of It: The Role of Telomeres in Fetal Origins of Adult Disease

“…To demonstrate the importance of telomerase activity in the oocyte, mice that are mTert −/−   have been used to show that it is imperative to have a functional telomerase enzyme for proper germ cell formation and fertility. Tert −/− mice display infertility due to numerous causes that are present in the human populations including impaired meiotic synapsis and recombination, with more germ cells preferentially arresting in early meiosis [56, 57]. Similar problems can occur in human infertility, which may show a link between telomerase activity, telomeres, and germ cell health [58].…”