Women carrying this genetic variant are at greater risk of miscarriage

One of the causes of spontaneous termination of pregnancy is the fact that the fertilized egg is aneuploid, that is, it has an abnormal number of chromosomes, and this is a phenomenon that tends to increase with age. ‘age. It is still poorly understood, because “knowledge of the precise genetic landscape underlying oocyte abnormalities in women is limited, as data on the subject are difficult to obtain and therefore absent from public genetic datasets”explain scientists from Rutgers University, in the United States.

Identify genetic factors

They wanted to carry out a study, published in the journal Proceedings of the National Academy of Sciences (PNAS) in October 2024, to identify the genetic determinants of reproductive aging via oocyte aneuploidy. So they began by performing a comprehensive computer analysis of genes with high egg aneuploidy, then reviewed data from a biobank from an in vitro fertilization (IVF) clinic. The scientists also looked for patterns in maternal DNA sequences that were collected from patients.

A genetic variant promotes spontaneous termination of pregnancy

“We identified 404 genes carrying variants enriched in adults with pathologically high oocyte aneuploidy rates”say the researchers. Their analysis made it possible to link egg aneuploidy to genes in the kinesin protein family. Specifically, a variant in the KIF18A kinesin protein gene was identified, which is distinguished from the non-mutated version by only one amino acid. And it is this mutation which accelerates the aging process of the eggs in young women who carry this genetic variant. This therefore damages their fertility and increases the risk of natural termination of pregnancy.

Scientists confirmed the results by conducting experiments on rodents that were genetically modified to carry this mutated gene. Carrier animals were confirmed to have more aneuploid eggs at an earlier age than normal. Leelabati Biswas, who is part of the team that conducted the study, explains in a press release: “We can say that this is not just a correlation, but a cause and effect relationship. The results allowed us to strongly validate our computational data. This is a first step “. And the discovery is important, because it could help women who want to have children: “If you know your genetic risk, you will know that your outcomes will be better if you start at 28 rather than 32. This can make a huge difference in your success.” From now on, she indicates that the team is continuing its work: “We are moving in a direction where we may be able to give women more opportunities for precision medicine, to better inform them, using targeted genetic information for reproductive treatments.”