A fertilised egg does not ensure successful reproduction in humans. Within days following fertilisation, the majority of embryos stop growing and die, typically due to an abnormally high number of chromosomes.
The majority of these faults, according to new research from Columbia University’s Vagelos College of Physicians and Surgeons, are caused by unintentional mistakes made during DNA replication during the first stages of cell division.
The research offers a fresh understanding of the fundamental biology of human reproduction and, in the long run, might increase the success rate of in vitro fertilisation (IVF). This study was published in the journal ‘Cell’. Cell division starts about 24 hours after a human egg has been fertilised.
The complete genome, which consists of 46 chromosomes and more than 3 billion base pairs of DNA, must be correctly replicated throughout cell division. The duplicate chromosomal sets must then be divided, giving each daughter cell a whole set.
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.
In order to comprehend normal and disease-causing changes in the human germ line, the researchers plan future investigations examining DNA damage during replication. These investigations may eventually result in techniques to lessen the chance of genetic anomalies and embryo attrition in patients undergoing IVF.