To ensure that the fetus is supplied with nutrients in the womb, the placenta increases the number of blood vessels. A study on mice now shows that signaling substances that are released by the fetus itself are crucial for this. For the baby’s healthy development, it is important that only one of the two gene copies that it received from the father and mother is active in the production of these signaling substances. Otherwise there is a risk of stunted growth. The study provides insights into the molecular interactions and enables a better understanding of pathological changes.
The placenta forms the connection between the mother and the unborn child during pregnancy. It arises from embryonic tissue that grows into the lining of the uterus and contains both fetal and maternal parts. In the course of pregnancy, more and more blood vessels form, which ensure that the baby receives nutrients from the mother via the placenta. If too few blood vessels are formed, this can lead to an insufficient supply and reduced growth of the child. An oversupply, on the other hand, is associated with rapid growth, malformations and tumors.
Growth factor of the fetus
A team led by Ionel Sandovici from the University of Cambridge has now used mice to research how the nutrient supply to the fetus is regulated at the molecular level. “As the fetus grows in the womb, it needs food from its mother, and healthy blood vessels in the placenta are important to get the right amount of nutrients,” explains Sandovici. “We found a way for the fetus to communicate with the placenta to get these blood vessels to form properly. If this communication is broken, the blood vessels will not develop properly and the baby will have difficulty getting the food it needs. “
According to the researchers, a key protein in this communication is the growth factor IGF2 (Insulin-like Growth Factor 2). In pregnant mice, they showed that this is secreted both by the fetus itself and by the placenta and the endothelial cells that line the blood vessels. For the growth of the blood vessels supplying the fetus, the IGF2, which it releases itself, is apparently the most important. When the researchers suppressed the production of fetal IGF2 in mice, the placenta formed fewer blood vessels and the unborn baby mice were poorly cared for. “We have known for some time that IGF2 promotes growth in the organs in which it is produced. In this study we showed that IGF2 also acts like a classic hormone – it is produced by the fetus, gets into the fetus’ blood, through the umbilical cord and to the placenta, where it works, ”says Sandovici.
“Tug of war” of genes
IGF2 is produced by reading the corresponding gene for it. Since every person receives one copy of the gene from the father and one from the mother, the gene is duplicated. However, so that too much IGF2 is not released, the maternal gene copy is normally shut down by epigenetic changes. This epigenetic inactivation is called imprinting. It was already known that imprinting disorders in which either none or both gene copies are activated can lead to serious genetic diseases in humans with tall or short stature.
Sandovici and his team have now investigated the underlying molecular mechanisms in more detail in mice. They found that the IGF2 receptor, which is required for IGF2 to work, is also produced by a gene of which only one of the two copies is active – in this case the maternal one. According to the researchers, this finding represents a kind of “tug of war” between the paternal and maternal genes of the fetus. Sandovici’s colleague Miguel Constância describes: “In our study, the copy of the gene for IGF2 inherited from the father drives the fetus’ demands for larger blood vessels and more nutrients, while the copy of the gene for the IGF2 receptor in the placenta, inherited from the mother, controls how much It provides nutrients. “
The balance thus maintained ensures that the fetus is neither too much nor too little cared for. The results can help to better understand possible disturbances in this process and, if possible, to treat medically.
Source: Ionel Sandovici (University of Cambridge) et al., Developmental Cell, doi: 10.1016 / j.devcel.2021.12.005