In humans, a fertilised egg does not guarantee successful reproduction. The majority of embryos stop developing and die within days of fertilisation, often due to an excessively large number of chromosomes. According to recent study from Columbia University’s Vagelos College of Physicians and Surgeons, the bulk of these flaws are created by inadvertent errors occurring during DNA replication during the initial stages of cell division.
The study contributes to a better knowledge of the underlying biology of human reproduction and, in the long term, may improve the success rate of in vitro fertilisation (IVF). The findings of this study were reported in the journal ‘Cell.’ Cell division begins around 24 hours after a human egg is fertilised.
Many human embryos made through IVF go awry, resulting in some cells having an abnormally high or low number of chromosomes.
According to study leader Dieter Egli, PhD, a Maimonides Assistant Professor of Developmental Cell Biology (in paediatrics) at Columbia University Vagelos College of Physicians and Surgeons, “duplicating the DNA is a tough challenge for the early embryo.”
The penultimate stage of cell division, when the double sets of chromosomes divide into two identical daughter cells, has long been thought by researchers to be the time when mistakes happen. The mechanism that separates the two sets of chromosomes, the microtubule spindle, was found to be the primary cause of the majority of these failures.
But according to Egli’s research, chromosomal defects result from mistakes that happen much earlier in cell division, when DNA from the genome is replicated. His research revealed that if the DNA is not duplicated properly, the spindle malfunctions and inserts the incorrect number of chromosomes into each daughter cell. The spindle does not operate normally when DNA duplication is aberrant. Why would the embryo allow the integrity of the genome to be disrupted when this is such a crucial prerequisite for normal development? This has mainly been ignored in prior studies. Egli claims.
Despite the fact that the trials involved embryos developed in a petri dish, including those from patients undergoing IVF and egg donors who were not seeking fertility treatment, the same issues may also affect embryos developed during normal human reproduction.
Obstacles within the double helix of the DNA appear to be the root of DNA copying mistakes in embryos. Despite the fact that the exact nature of these barriers is unknown, they cause DNA duplication to stall or even cease, which leads to DNA breakage and an abnormal number of chromosomes.
The researchers discovered that spontaneous DNA mistakes can happen during the first cell division cycle in human embryos, as well as during subsequent cell divisions. The embryo cannot develop further if there are too many chromosomally defective cells in the early embryo.
The majority of human embryos produced through IVF stop growing a few days after conception. The effectiveness of reproductive therapies is hampered by the inefficiency of human development.
“Many women receiving fertility treatment need several IVF rounds to become pregnant, and some of them never do. This is extremely expensive and draining emotionally, “says co-author of the study and reproductive specialist Jenna Turocy, MD, of the Columbia University Fertility Center.
Future studies will look at DNA damage during replication to better understand normal and disease-causing alterations in the human germ line. These findings may eventually lead to procedures that reduce the likelihood of genetic abnormalities and embryo attrition in IVF patients.