The International Journal of Developmental Biology

Int. J. Dev. Biol. 56: 841 - 852 (2012)

Vol 56, Issue 10-11-12

Special Issue: Female Germ Cells in Development & Tumors

Oocyte ageing and its cellular basis

Published: 29 January 2013

Ursula Eichenlaub-Ritter

University of Bielefeld, Faculty of Biology, Institute of Gene Technology/Microbiology, Germany


Aneuploidy is extremely high in aged human oocytes. Its cellular origin has been elusive. Trisomy data implicate predominantly meiosis I errors in the genesis of oocyte aneuploidy. Susceptible recombination patterns increase risks for nondisjunction. Cytogenetic analyses of aged human oocytes and embryos from assisted reproduction (ART) suggest that aneuploidy primarily relates to precocious chromatid separation. Oocytes express a spindle assembly checkpoint (SAC), but do not arrest maturation in the presence of improperly attached or single, unattached chromosomes. The SAC may be more permissive by altered gene expression in aged oocytes. Aged oocytes frequently exhibit precocious loss of chromosome cohesion. In experimental models, cohesion cannot be restored once lost, a process possibly occurring during long meiotic arrest. Maternal age, hormonal stimulation, disturbed metabolism, and depletion of the follicle pool contribute to mitochondrial dysfunction, spindle aberrations, and errors in chromosome segregation. Caloric restriction and antioxidants reduce mitochondrial dysfunction and aneuploidy in aged rodent’s oocytes. Loss of chromosome cohesion appears to be a major risk factor for aneuploidy by disturbing the sequential separation of homologs and chromatids. A permissive SAC, the presence of risky meiotic exchanges, changes in expression, and failures to resolve improper chromosome attachments, as well as mitochondrial dysfunction may synergistically increase susceptibility to meiotic errors. A healthy life style, mild stimulation and an optimal environment may delay ageing and sustain control over chromosome disjunction, whereas loss of cohesion appears to be irreversible.


oocyte, ageing, aneuploidy, spindle, chromosome cohesion

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