The developing fetus is more susceptible to external influences than previously thought. A new study, published in Science Advances, shows that factors such as stress could affect the development of the fetal brain.
"We are interested in how factors in the environment affect the developing brain, especially in the prenatal period. Previously, it was assumed that the uterus was like a bubble where nothing could get through. We now know that's wrong. We are on a mission to find out what early life exposure to different factors could do to a human, focusing on brain development," says Cristiana Cruceanu , assistant professor at the Department of Physiology and Pharmacology , Karolinska Institutet.
The international team of researchers from Karolinska Institutet, the Max Planck Institute of Psychiatry, and Helmholtz Munich, wanted to find out how glucocorticoids, a part of the body's natural stress response and an essential part of normal fetal development, affect the development of the human brain when overexposed.
Modelling of the brain in vitro
For instance, if there is a risk of pre-term delivery, synthetic glucocorticoids are often prescribed during pregnancy to promote lung development. But how do these synthetic glucocorticoids affect the fetal brain?
To find that out, the researchers used brain organoids, three-dimensional models of the developing brain, derived from human stem cells and matured in a petri dish.
That way they could simulate excessive exposure during early pregnancy. This state-of-the-art technology allows researchers to use a human specific system to understand these processes, without discomfort or harm to real humans or animals.
Exposure shapes the brain
The researchers found that excessive exposure to glucocorticoids does shape the fetal brain. They saw a shift in the distribution of neuron types: In the exposed organoids, there was a higher proportion of inhibitory neurons and a lower proportion of excitatory neurons than in the unexposed organoids.
These findings show that the developing brain is susceptible to external influence.
"We see an increased amount of inhibitory neurons, but our study results do not show whether this means an increased risk or resilience to certain disorders later in life," Cruceanu explains.
"We know that stress, depression and anxiety during pregnancy are common, and that the need for treatment with medications like antidepressants comes in. Therefore, current work in my lab aims to study the effects of such medications on the developing brain. We want to know: Can the potentially negative effects of maternal stress be counteracted by antidepressant medications in the developing child - as it works for the mother? This is a complicated question to answer, but with organoids we can control the exposure paradigms and look specifically at brain development", concludes Cristiana Cruceanu.
Publication
" Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids | Science Advances ", Leander Dony, Anthi C. Krontira, Lea Kaspar, Ruhel Ahmad, Ilknur Safak Demirel, Malgorzata Grochowicz, Tim Schäfer, Fatema Begum, Vincenza Sportelli, Catarina Raimundo, Maik Koedel, Marta Labeur, Silvia Capello, Fabian J.Theis, Cristiana Cruceanu and Elisabeth B. Binder. Science Advances, online 14 February 2025, doi: 10.1126/sciadv.adn8631.
