Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos

Abstract

Telomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.

Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications

“…Reduced methylation destabilizes heterochromatin at pericentromeric regions and is associated with loss of tumor suppression and oncogenesis in gastrointestinal cancers and sarcomas [21,22]. Telomere length is affected by methylation of sub-telomeric regions, and its dysregulation is considered a cancer hallmark [21,24,25].…”

Facilitation of Ovarian Response by Mechanical Force—Latest Insight on Fertility Improvement in Women with Poor Ovarian Response or Primary Ovarian Insufficiency

“…Advancing age can also lead to increased damage of telomeres and genomic DNA in oocytes and granulosa cells [78][79][80][81], and age-related epigenetic status has been linked to low oocyte yield and poor ovarian response in IVF patients [82,83]. Telomeres play a central role in determining cell fate and aging in every organ.…”

“…A few hundred nucleotides of telomere repeats must "cap" each chromosome end to maintain genomic stability. When too many "uncapped" telomeres accumulate in aging oocytes, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis [78][79][80]. Studies of oocytes and ovarian somatic cells indicate that telomere length and telomerase activity exhibit dynamic changes during oocyte maturation and early embryo development, and that measurements of telomere length and telomerase activity in polar body, cumulus cells, and granulosa cells could help predict the developmental potential of oocytes and embryos [79].…”

“…When too many "uncapped" telomeres accumulate in aging oocytes, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis [78][79][80]. Studies of oocytes and ovarian somatic cells indicate that telomere length and telomerase activity exhibit dynamic changes during oocyte maturation and early embryo development, and that measurements of telomere length and telomerase activity in polar body, cumulus cells, and granulosa cells could help predict the developmental potential of oocytes and embryos [79]. Excessive telomere shortening may contribute to miscarriage and birth defects in aging women, perhaps due to reduced synapsis and chiasma or abnormal meiotic spindle assembly [80,84].…”