Stressed dads can affect offspring's brain development

Stress felt by dad-whether as a preadolescent or adult-leaves a lasting impression on his sperm that gives sons and daughters a blunted reaction to stress, a response linked to several mental disorders, according to a new study.

The findings point to a never-before-seen epigenetic link to stress-related diseases such as anxiety and depression passed from father to child.

While environmental challenges, like diet, drug abuse, and chronic stress, felt by mothers during pregnancy have been shown to affect offspring neurodevelopment and increase the risk for certain diseases, dad's influence on his children are less well understood. The effects of lifelong exposures to dad on children are even more out of reach.

Now, a team of researchers led by Tracy L. Bale, PhD, associate professor of neuroscience in the Perelman School of Medicine Department of Psychiatry and the School of Veterinary Medicine Department of Animal Biology have shown that stress on preadolescent and adult male mice induced an epigenetic mark in their sperm that reprogrammed their offspring's hypothalamic-pituitary-adrenal (HPA) axis, a region of the brain that governs responses to stress.

Surprisingly, both male and female offspring had abnormally low reactivity to stress.

This stress pathway dysregulation-when reactivity is either heightened or reduced-is a sign that an organism doesn't have the ability to respond appropriately to a changing environment. And as a result, their stress response becomes irregular, which can lead to stress-related disorders.

Researchers found that offspring from paternal stress groups displayed significantly blunted levels of the stress hormone corticosterone-in humans, it's cortisol-in response to stress.

To understand the neural circuitry in the offspring, the group also examined changes in gene expression in certain brain regions involved in stress regulation: the paraventricular nucleus (PVN) and the bed nucleus of stria terminals.

They found an increased expression of glucocorticoid-responsive genes in the PVN, a change that supports a possible mechanism whereby increased negative feedback sensitivity may be explained.

The researchers also looked at a series of microRNAs (miRs) in the sperm that uniquely contribute to post-fertilization gene expression to examine the epigenetic mechanisms of transmission to the next generation. In both groups of stressed dads, there was a significant increase in expression of nine miRs.

These miRs may be targeting the stored maternal messenger RNAs in the egg at fertilization, so that dad's sperm can regulate some aspect of early development to inform his offspring about the environment, according to the authors.

They also point out that a reduced physiological stress response may reflect some adaptive evolutionary benefit passed on to offspring to ensure survival in what is expected to be a more stressful environment.

The findings were published in the Journal of Neuroscience.