It has been known for years that certain environmental factors—such as stress during pregnancy—can influence a baby’s development later on in life. On April 4th at the British Neuroscience Association Festival of Neuroscience in London, researchers presented very interesting findings on a possible mechanism negatively affecting fetuses. According to an article in Science Daily, Professor Megan Holmes, a neuroendocrinologist from the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science in Scotland (UK), has discovered a possible mechanism whereby a fetus’ exposure to high levels of stress hormones can result in mood disorders later in life.
Professor Holmes used genetic engineering in Rodents–the process of adding, removing, or manipulating a part of an animals genome via Biotechnology–to remove an enzyme she believed to be vital in correct pre-natal development. Holmes hoped to test how high levels of stress hormones affected both fetuses and puberty-age rodents—another time when drastic changes in development occur.
The Cellular Mechanics
According to Holmes, increased levels of Glucocorticoids—the steroid hormones that increase a result of stress or abuse– might directly affect the programming of fetal cells, raising the chances of problems later on. The steroid, Cortisol, is believed to be a key factor in the fetal cell programing, for it reduces growth, changes tissues, and has long-term effects on gene expression (Davis, 2010).
The enzyme, 11β-HSD2 (11beta-hydroxysteroid dehydrogenase type 2), usually found in the placenta and the fetal brain, has been implicated in breaking down Cortisol to inactive form, subsequently preventing it from harming a fetus during growth (Kajantie, 2003). By genetically engineering the mice to not have 11β-HSD2, and exposing them to high levels of stress hormones, Holmes was able to test if too little 11β-HSD2—or, better put, too much active Cortisol—was causing negative changes in programming.
What Holmes Found
The high levels of stress hormones directly reduced fetal growth and led to mood disorders later in life. More-so, the placentas of these 11β-HSD2 knockout mice were smaller, making nutrient transport more difficult in the developing fetus. Holmes therefore suggests that the placental 11β-HSD2 is key in inhibition of later mood disorders, acting as a shield to harmful stress hormones.
Holmes further states “preliminary new data show that with the loss of the 11ß-HSD2 protective barrier solely in the brain, programming of the developing foetus still occurs, and, therefore, this raises questions about how dominant a role is played by the placental 11ß-HSD2 barrier. This research is currently ongoing and we cannot draw any firm conclusions yet.”
You may think this is all great, yet Holmes bring an important issue to question: What implications do these findings have on current treatments? Specifically, for the past 20 years or so, we have treated pregnant mothers expected to prematurely deliver with dosages of synthetic glucocorticoids to stimulate fetal lung development. In trying to enhance the probability of life upon early birth, we may be causing irreversible mood disorders in children later on. Homes emphasizes “while this glucocorticoid treatment is essential, the dose, number of treatments and the drug used, have to be carefully monitored to ensure that the minimum effective therapy is used, as it may set the stage for effects later in the child’s life.”
What About Adolescence?
Holmes and her colleagues then decided to look at the affect of stress during early teenage years on mood and emotional behavior. They trained rats to respond to a specific learned task, and then exposed them to stressful environments, postulating that high levels of glucocorticoids released during times of stress may cause changes in the brains neural networks associated with emotional processing.
The fMRI (Functional Magnetic Resonance Imaging) results successfully “showed that in stressed ‘teenage’ rats, the part of the brain region involved in emotion and fear (known as amygdala) was activated in an exaggerated fashion when compared to controls.” Therefore, “altered emotional processing occurs in the amygdala in response to stress during this crucial period of development.”
Holmes emphasizes that “determining the exact molecular and cellular mechanisms that drive fetal programming will help us identify potential therapeutic targets that can be used to reverse the deleterious consequences on mood disorders. In the future, we hope to explore the potential of these targets in studies in humans.” Additionally, she hopes the results will promote awareness that “children exposed to an adverse environment, be it abuse, malnutrition, or bereavement, are at an increased risk of mood disorders” later, and the “children should be carefully monitored and supported to prevent this from happening.”
-Adapted from Science Daily Article
– Abstract title: “Perinatal programming of stress-related behaviour by glucocorticoids”.
– Symposium: “Early life stress and its long-term effects-experimental studies”, at 15.15 hrs BST on Sunday 7 April, Cinema 1.