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.
"It didn't matter if dads were going through puberty or in adulthood when stressed before they mated. We've shown here for the first time that stress can produce long-term changes to sperm that reprogram the offspring HPA stress axis regulation," said Bale. "These findings suggest one way in which paternal-stress exposure may be linked to such neuropsychiatric diseases."
Past epidemiological studies suggest that germ cells — sperm and eggs — are more susceptible to reprogramming during the slow growth period of preadolescence. Therefore, in this study, in order to examine the effects of paternal stress, male mice were exposed to six weeks of chronic stress, before breeding, either throughout puberty or only in adulthood. Examples of stress include sudden move to another cage, predator oder (fox urine, for example), noise, or a foreign object in the cage.
Male mice are ideal for such an experiment because they do not participate in offspring rearing, meaning any external factors outside of germ-cell formation are essentially eliminated.
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.