Mechanisms and Consequences of Mitotic Mis-Segregation During Early Embryogenesis

Abstract

Investigations into the relatively high frequency of spontaneous miscarriages have revealed that chromosomal instability (CIN) is common in human preimplantation embryos. This instability is characterised by an elevated rate of missegregation of whole chromosomes or parts of chromosomes during mitosis, often resulting in aneuploidy. Aneuploidy is a condition marked by an aberrant chromosome number in a cell and is particularly evident in the initial three cleavages following fertilization. Interestingly, these observations provide valuable insight into the challenges associated with successful fertility rates. However, the underlying mechanisms driving early-stage embryonic aneuploidy and the fate of aneuploid embryos remain unclear. Suggestions of protective mechanisms that act against aneuploid cells, including apoptosis, preferential allocation, and trisomic rescue, among others, have been proposed. Here again, a comprehensive understanding of these mechanisms is still lacking. This review therefore aims to elucidate the established and strongly indicated causal mechanisms of preimplantation embryo aneuploidy known thus far and discuss the potential consequences and outcomes of impacted embryos. Exploring these mechanisms is crucial for advancing our understanding of human fertility and is instrumental in improving the success rates of human IVF by unveiling potential targetable mechanisms that are capable of mitigating aneuploidy.