Hormones produced during pregnancy cause significant changes throughout the body, including adjustments in the function and condition of the uterus to support fetal growth. However, the impact of pregnancy on the brain and its role in helping the body adapt to this state has not been thoroughly studied. American neurobiologists conducted research to find out how the brain participates in maintaining pregnancy.

Interaction of Body Systems During Pregnancy

For pregnancy to progress successfully, various body systems must work together in harmony. After fertilization, the embryo must attach to the endometrium—the inner lining of the uterus. During this period, numerous changes occur: metabolism, immune system, and hormonal regulation are all restructured, which is essential for the normal development of the fetus.

However, sometimes pregnancy is interrupted, and the cause is not always clear. About half of early miscarriages are linked to chromosomal abnormalities in the embryo, but in other cases, it is difficult to determine a single reason.

The Role of the Brain in Maintaining Pregnancy

Researchers hypothesized that some processes affecting the course of pregnancy may be connected not only to the uterus and embryo but also to the brain, which coordinates the body's functions during this period.

The team of neurobiologists studied gene activity in the brains of pregnant mice and identified a type of neuron whose removal prevented the embryo from attaching to the uterus. Four populations of neurons expressing the Esr1 gene (which encodes the estrogen receptor α) were examined, and some of these also expressed the progesterone receptor. These neurons are located in different brain regions previously associated with ovulation, sexual behavior, and maternal care, but their role in supporting pregnancy remained unclear.

Genetic Changes in Neurons During Pregnancy

In the experiment, mice on the 14th day of pregnancy were used, at which point normal embryo development was confirmed. Using single-nucleus RNA sequencing, researchers identified changes in the activity of 2,788 genes across four neuron populations, of which 1,709 coded for proteins.

Changes in gene activity affected different brain regions in various ways: most genes altered their activity only in a specific area or neuron group. Only three genes changed activity in the same way across all studied groups. This suggests that pregnancy does not trigger a single program of changes in the brain—different neuron groups adapt individually depending on their location and function. In some cases, neurons acquired a new molecular profile.

The Special Role of POANpy2r Neurons

In the preoptic area of the hypothalamus, a special type of GABAergic neuron expressing the Npy2r gene (the Y2 neuropeptide receptor) was identified. During pregnancy, gene activity in these cells changed especially strongly.

This is not about the appearance of new neurons, but rather the restructuring of existing cells. In females without offspring, this type of neuron was also present, but during pregnancy, the cells acquired different properties.

Experiment on Neuron Removal

To test the significance of these neurons, genetically modified Npy2rCre mice were used. A viral construct with caspase-3, which causes cell death in Npy2r receptor cells, was introduced into the preoptic area of the hypothalamus. Only animals in which the number of such cells was reduced by more than 70% were included in the analysis.

Two groups of females—modified and control—were paired with males, and their condition was monitored. Removal of POANpy2r neurons did not affect sexual behavior, ovulation, or fertilization: the females mated normally, fertilization occurred, and zygotes formed.

However, further observation revealed that in mice lacking these neurons, embryos did not implant in the uterus, causing pregnancy to terminate at an early stage.

The Significance of the Results

Thus, these neurons are not responsible for conception itself, but are necessary for successful embryo implantation and the continued maintenance of pregnancy after fertilization.

The researchers also found a similar group of neurons in the preoptic hypothalamus of an adult woman by studying the gene activity map in the human brain. However, it has not yet been proven that these cells perform the same function in humans, since conducting a similar experiment in pregnant women is impossible. The role of these neurons will need to be studied by other methods.

The scientific study was published on the bioRxiv biology preprint website.