Reacción a "A large study finds genetic variants associated with pregnancy loss"

Meiosis is the cell division process that occurs in eggs and sperm. Thanks to this mechanism, one cell with two copies of each chromosome gives rise to four cells with only one copy each. This process is essential for maintaining a constant number of chromosomes between generations and for generating genetic variability.

In women, meiosis begins before birth, during fetal development. At that time, the chromosomes pair up and exchange fragments of DNA in a process called recombination. However, meiosis stops and remains paused for years, until ovulation and, potentially, fertilization occur. During this long waiting period, problems can arise in the mechanisms that hold the chromosomes together. If this attachment fails, the chromosomes can separate prematurely, resulting in eggs with an incorrect number of chromosomes when meiosis resumes.

This incorrect chromosome segregation is one of the main causes of early pregnancy loss. It is estimated that around 15% of recognized pregnancies end in miscarriage, and many other conceptions are lost at very early stages without ever being detected. For years, it has been known that the most frequent cause is the presence of extra or missing chromosomes, a condition known as aneuploidy.

Despite this knowledge, it is still poorly understood how genetic differences between individuals influence these molecular processes. It is also unclear to what extent factors other than age, such as individual genetics, can predispose a woman to produce eggs with chromosomal abnormalities. To answer these questions, it is necessary to analyze the genetic information of a large number of embryos before pregnancy loss, as well as that of their parents.

In this context, the team led by Rajiv McCoy, a computational biologist at Johns Hopkins University, recently published a study in the journal Nature. The research was co-led by Sara Carioscia, a graduate student and first author of the paper, and Arjun Biddanda, a postdoctoral researcher.

The team analyzed data from embryos obtained through in vitro fertilization and compared the embryos' DNA with that of their biological parents. In total, they studied approximately 139,000 embryos from 23,000 couples. To manage this enormous amount of information, they developed a computer program that allowed them to identify relevant genetic patterns and associations.

Thanks to this large-scale analysis, the researchers were able to link certain maternal genetic variants to characteristics of chromosomal crossover and the risk of aneuploidy. The results revealed a shared genetic basis involving key genes in meiosis.

The study showed clear connections between specific variations in the mother's DNA and the likelihood that her embryos would not be viable. Unexpectedly, the same genetic variants associated with a higher risk of miscarriage were also linked to recombination, the process that generates genetic diversity in eggs and sperm.

The strongest associations were found in genes that control how chromosomes pair up, exchange genetic material, and remain attached during egg formation. Among these, the SMC1B gene stands out; it encodes a protein that is part of a ring-shaped structure that surrounds and holds chromosomes together. These structures are essential for proper chromosome segregation and tend to deteriorate with age.

Taken together, the results indicate that inherited genetic differences in these meiotic processes contribute to the natural variation in the risk of aneuploidy and miscarriage among individuals. This work provides the strongest evidence to date that common genetic variants can make some women more vulnerable to pregnancy loss.

However, the authors emphasize that, although genes related to miscarriage have been identified, it is still difficult to predict individual risk. This is because each common genetic variant usually has a very small effect compared to factors such as maternal age or environment. Even so, these genes represent promising targets for the development of future treatments.

Currently, the team is investigating rare genetic variants in both mothers and fathers that could have a more pronounced effect on the risk of aneuploidy. They are also using new technologies to better understand how subtle genetic changes can influence early pregnancy loss.

Taken together, these findings provide new insights into human reproduction and open potential avenues for developing treatments that reduce the risk of pregnancy loss. Furthermore, they deepen our understanding of the earliest stages of human development and lay the groundwork for future advances in reproductive genetics and fertility medicine.