Analysis of data from 140,000 embryos obtained in vitro: common variants in maternal genes make you more vulnerable to losing a pregnancy.
A genetic study on the data of almost 140,000 embryos has made it possible to trace new factors at the origin of early and involuntary terminations of pregnancy. Based on research, conducted by scientists at Johns Hopkins University and published in Naturespecific and common variations in maternal genes would be linked to a higher risk of miscarriages. And they may partly explain why only half of conceptions ultimately result in a birth. The authors of the study hope that the results will be useful for organizing specific interventions for patients at risk, so as to reduce the occurrence of spontaneous pregnancy losses.
Pregnancy, a bumpy ride
About 15% of confirmed pregnancies end in miscarriage, but the loss of the zygote, the cell obtained during conception, can occur even before implantation in the uterus, before the pregnancy is discovered. The main reason for these early losses are extra or missing chromosomes; in fact, only a few chromosomal anomalies allow the survival of the fetus and the successful conclusion of the pregnancy. One of these is Down syndrome or trisomy 21, a genetic condition caused by an extra copy of chromosome 21.
Most of these anomalies originate in the egg cell, and their frequency increases as the mother’s age increases. However, less known are the factors other than age that can predispose a woman to produce egg cells with an abnormal number of chromosomes.
Missing cohesion
The study shed light on these age-independent factors. And it found that variations in genes that govern how chromosomes pair, recombine and hold together during egg formation show the strongest associations with the risk of early and spontaneous pregnancy loss.
In particular, there is a high risk of producing embryos that will not survive for those carrying variations in the SMC1B gene, which codes for a part of the ring structure that keeps the chromosomes united and cohesive during the preparation for cell division. This structure is fundamental to ensure correct segregation of chromosomes in daughter cells and deteriorates with age: separation errors in chromosomes can cause chromosomal abnormalities, and are more common if pregnancy occurs at an advanced age.
Risks and benefits
Ironically, the same genetic variants that influence the risk of miscarriage are also associated with a fundamental process of genetic shuffling that occurs during sexual reproduction – gene recombination, which extends the genetic variability of a population because it generates diversity when eggs and sperm are created.
The discovery was possible thanks to the analysis of the DNA of the embryos and the 23,000 pairs of parents who had produced them through a computer program that detected recurring patterns in this enormous amount of data. The hypothesis is that problems in the mechanism that holds chromosomes together occur during the many years of “pause” in meiosis, the cell division necessary for reproduction. This process begins during fetal development and then resumes decades later during fertilization. Hereditary differences in the genes that govern it can have an important impact on the success of future pregnancies.
