During his lifetime, a father's experience of stress can alter his sperm in ways that impact the development of his offspring — including their brains and how they themselves respond to stress.
A study that was presented recently at the 2018 annual meeting of the American Association for the Advancement of Science, held in Austin, TX, reveals fresh insights into how this happens.
It has already been established that a mother's experience during pregnancy — including the quality of her diet, stress, and infection — can influence the development of her offspring, including their brains.
The new research — which was led by Tracy Bale, who is a professor of pharmacology at the University of Maryland School of Medicine in Baltimore — increases our understanding of how fathers can also influence the brain development of their offspring.
The study, which is yet to be published, concerns the field of epigenetics, relating to factors that can alter the instructions held in our DNA code without changing the code itself.
Epigenetics, health, and disease
Epigenetic changes play an important role in health and disease. For instance, they can change what happens in cells by switching genes on and off and by determining which proteins are produced.
Furthermore, there is mounting evidence from epigenetics regarding how the environmental exposures and experiences of one generation can influence the biological development and disease risks of the next through mechanisms of inheritance.
Cancer was one of the first human diseases that researchers linked to epigenetic changes.
Studies from as early as the 1980s found that tumor tissue from people with colorectal cancer had fewer epigenetic markers known as DNA methylation than normal tissue from the same individuals.
The new study reveals the process through which a lifetime of mild stress in male mice can change specific epigenetic markers in their sperm to shape brain development and impair the stress response of their offspring.
Epigenetic changes and microRNAs
In previous work, Prof. Bale — then at the University of Pennsylvania in Philadelphia — discovered that the epigenetic changes are conveyed through microRNAs, a family of molecules that can turn genes on and off. While they do not code for proteins, microRNAs can influence their production.
That work showed that offspring fathered by adult mice that had experienced "chronic periods of mild stress" had an impaired stress response.
Examples of mild stress challenges included moving the animals to new cages and exposing them to the urine of a predator species, such as that of foxes.
At the meeting, Prof. Bale presented her latest work, in which she uncovered the biological mechanism that allows changes in the father's microRNA to be passed onto his offspring.
Vesicles holding microRNAs fuse with sperm
Once male sperm forms in the testes, it travels to the caput epididymis, where it matures. A part of the maturing process involves fusing the male "germ cells" with tiny sacs, or vesicles, produced by the caput epididymis.
The vesicles that are fused to the sperm contain microRNAs — including those that may have changed as a result of the father's stress experience. These microRNAs ultimately influence gene expression in the offspring.
The findings suggest that even mild stress challenges in fathers can result in a noticeable change in the development, and therefore health, of their offspring.
The hope is that by learning more about these underlying hereditary mechanisms, we stand a better chance of being able to treat and prevent some of the diseases that they contribute to.