A Versatile Cohesion Manipulation System Probes Female Reproductive Age-Related Egg Aneuploidy
As women age, the quality of their eggs can decline, often leading to a higher risk of aneuploidy—a condition where eggs have an abnormal number of chromosomes. This is a major factor in age-related infertility and miscarriage. Scientists have long suspected that a gradual weakening of “cohesion,” the glue that holds chromosomes together, contributes to this problem. However, precisely how this happens has been unclear, partly because other factors like issues with the cell’s internal scaffolding can also play a role.
To better understand this complex process, a new research tool was developed. This innovative system allows scientists to precisely control and reduce the levels of a key cohesion protein, called REC8, in live mouse egg cells. Think of it like having a dimmer switch for the chromosomal glue, enabling researchers to observe the effects of varying “stickiness” in real-time.
Using this system, a crucial discovery was made: the premature separation of sister chromatids (the two identical halves of a chromosome) doesn’t just gradually increase as cohesion weakens. Instead, it sharply escalates only when the REC8 protein levels drop below a specific, critical point. This finding supports a “threshold model,” suggesting there’s a certain limit to how much cohesion can be lost before the egg becomes highly vulnerable to chromosomal errors. This breakthrough provides a clearer understanding of why egg aneuploidy dramatically rises with advanced reproductive age and offers a valuable platform for future research into potential treatments.
Source: link to paper