Investigating the causes of genome instability in development

Fertility treatments often fail because embryos can struggle to develop properly due to genome instability in vitro. An observed slowdown in DNA copying can lead to what is known as DNA replication stress, which often results in detrimental chromosomal abnormalities. Compared to other mammals, human embryos are more susceptible to these chromosomal errors, which can occur not only before but also after fertilization, during the first stages of the embryo's cell division. These mistakes in copying the DNA can disrupt normal development, result in miscarriage and disease. The investigators at Columbia University found that certain metabolites can cause DNA replication stress and genome instability in cancer cells. The team hypothesizes that there may be parallels in early human development and they plan to test this hypothesis experimentally. Their goals are to understand the causes of DNA replication stress, the full range of its consequences, and learn how to prevent the formation of chromosomal and genetic abnormalities in embryos. Understanding the root causes and consequences of DNA replication stress, as well as developing strategies to mitigate it, could translate to clinical advances, including higher success rates in fertility treatments using fewer oocytes and hormonal cycles.