An emerging area of study involves the role by which prenatal exposure to environmental factors can influence fetal development and increase the chance of physical or mental problems later in life.
Megan Holmes, Ph.D., a neuroendocrinologist from the University of Edinburgh, believes her research using mice provides an answer to how this occurs.
“During our research we have identified the enzyme 11ß-HSD2 which we believe plays a key role in the process of fetal programming,” she said.
Adverse environments experienced while in the womb, such as stress, bereavement or abuse, will increase levels of glucocorticoid hormones in the mother, which may harm the growing baby.
“The stress hormone cortisol may be a key factor in programming the fetus, baby or child to be at risk of disease in later life. Cortisol causes reduced growth and modifies the timing of tissue development as well as having long lasting effects on gene expression,” Holmes said.
Holmes’ research has identified an enzyme called 11ß-HSD2 that breaks down the stress hormone cortisol to an inactive form, before it can cause any harm to the developing fetus.
The enzyme 11ß-HSD2 is present in the placenta and the developing fetal brain where it is thought to act as a shield to protect against the harmful actions of cortisol.
Holmes and her colleagues developed genetically modified mice that lacked 11ß-HSD2 in order to determine the role of the enzyme in the placenta and fetal brain.
“In mice lacking the enzyme 11ß-HSD2, fetuses were exposed to high levels of stress hormones and, as a consequence, these mice exhibited reduced fetal growth and went on to show programmed mood disorders in later life,” she said.
“We also found that the placentas from these mice were smaller and did not transport nutrients efficiently across to the developing fetus. This too could contribute to the harmful consequences of increased stress hormone exposure on the fetus and suggests that the placental 11ß-HSD2 shield is the most important barrier.”
However, researchers say that new preliminary data shows that even when the 11ß-HSD2 protective barrier is absent, programming of the developing fetus still occurs.
“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,” Holmes said.
Holmes hopes that her research will inform health professionals on the danger of an adverse prenatal environment, be it abuse, malnutrition, or bereavement, and for the increased risk of mood disorders in later life.
She said children should be carefully monitored and supported to prevent this from happening.
In addition, the potential effects of excessive levels of stress hormones on the developing fetus are also of relevance to individuals involved in antenatal care.
Within the past 20 years, the majority of women at risk of premature delivery have been given synthetic glucocorticoids to accelerate fetal lung development to allow the premature babies to survive early birth.
“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,” she said.
Puberty is another sensitive time of development and stress experienced at this time can also be involved in programming adult mood disorders. Holmes and her colleagues have found evidence from imaging studies in rats that stress in early teenage years could affect mood and emotional behavior via changes in the brain’s neural networks associated with emotional processing.
“We showed that in stressed ‘teenage’ rats, the part of the brain region involved in emotion and fear (known as the amygdala) was activated in an exaggerated fashion when compared to controls.
“The results from this study clearly showed that altered emotional processing occurs in the amygdala in response to stress during this crucial period of development.”
Source: British Neuroscience Association