Study brings new clues about the genetic factors associated with aneuploidy, an anomaly in the number of chromosomes in cells and one of the most frequent causes of pregnancy loss.
Pregnancy loss continues to be a common phenomenon around the world. About 15% of known pregnancies end in miscarriage, although the true number is probably higher as many losses occur before the pregnancy is detected.
Recently, a study in Nature brought new clues about the genetic factors associated with aneuploidiaan abnormality in the number of chromosomes in cells and one of the most frequent causes of pregnancy loss. According to researchers, about half of known miscarriages in the first or second trimester are associated with embryos with more or less chromosomes.
To better understand the origin of these chromosomal errors, a team led by Rajiv McCoya computational biologist at Johns Hopkins University, analyzed genetic data from nearly 140,000 embryos resulting from fertilization in vitro. The objective was to identify how common genetic variations can influence the risk of some parents generating non-viable embryos, explains .
According to McCoy, this work provides the clearest evidence yet about the molecular pathways through which differences in the risk of chromosomal errors arise in humans. Chromosomal abnormalities usually appear in the egg and become more frequent with maternal age, a known risk factor. However, the researchers emphasize that the broader genetic context remained poorly understood, in part due to the lack of large enough databases. As these genetic variations have small effects, very large samples are needed to detect them.
The team used clinical data from pre-implantation genetic testing done on fertilization embryos. in vitro. In total, 139,416 embryos from 22,850 pairs of biological parents were analyzed. The researchers identified 92,485 aneuploid chromosomes in 41,480 embryos. The strongest associations were found in genes involved in how chromosomes pair, recombine, and organize during meiosis in egg precursor cells.
One of the highlighted genes was SMC1Bwhich encodes a protein essential for keeping chromosomes together during this process. A variant of this gene has been associated with a reduction in the number of recombinations and an increase in aneuploidy of maternal origin. The study also identified links to other genes associated with chromosomal recombination, such as C14orf39, CCNB1IP1 e RNF212.
For McCoy, it is particularly relevant that these genes coincide with those that experimental research in model organisms, such as mice and worms, had already shown are crucial for recombination and chromosomal cohesion.
Female meiosis begins during fetal development, before birth, when chromosomes pair and recombine. Then, the process is interrupted for years, until it is resumed later, during ovulation and fertilization. Genetic variations can affect this prolonged suspension phase and increase the likelihood of incorrect chromosome separation.
The results deepen knowledge about the earliest stages of human development and can guide investigations and contribute to the development of new approaches in reproductive medicine.
