Ageing and aneuploidy in oocytes.

Abstract

Correlations between maternal age and Down syndrome have been known already for over half a century (Penrose 1933; Bond and Chandley 1983). Still, the reasons for the dramatic increase in risks for a trisomic conceptus, spontaneous abortion associated with a chromosomally unbalanced embryo and the significantly reduced developmental potential of oocytes and embryos in aged women are unclear. Demographic analysis shows that there still is a trend for delaying childbearing to advanced maternal ages in many industrialized countries. Accordingly, it has been estimated that 25% of conceptions will involve women of 35 years or older in the Netherlands in 2005–2009 (te Velde and Pearson 2002). Many couples attending the infertility clinics are of advanced age. Therefore, it is important to investigate the origin of the maternal age-related decline in fertility associated with aneuploidy in oocytes in order to predict individual risks and, possibly, improve treatment. This contribution reviews briefly the current status of research on the incidence and the origin of aneuploidy in aged oocytes in humans and some experimental animals The observations suggest that prenatal events in oogenesis and recombination patterns influence susceptibility of chromosomes to errors in segregation, but that the depletion of the follicle pool, hormonal homeostasis, the oocyte-specific fragility of cohesion between homologues and permissive cell-cycle regulation at maturation may be important in the reduced quality of aged oocytes, which affects critically the fidelity of chromosome segregation and developmental potential.