When it comes to reproductive health, it’s no secret that a pregnant mother’s choices and environment can severely impact her child’s epigenetics and health—especially mothers suffering from PTSD. But it turns out fathers who have suffered significant stress early on in their life may also epigenetically impact the physical and mental health of their offspring. It was previously thought that fathers only passed DNA to the mother’s egg during fertilization, but it was recently discovered that sperm also contributes miRNA, which could epigenetically impact the next generation.
Epigenetics is the study of heritable changes in gene expression that leave the underlying DNA sequence unchanged. These adjustments can occur due to environmental factors, diet, and stress and can have a lasting impression on an individual and their future generations.
A recent study out of Tufts University demonstrates that early trauma in male mice leads to epigenetic changes in sperm miRNA, resulting in poor mental and physical health of their offspring, and the same may be said for humans.
The research team led by Dr. Larry Fieg and M.D./Ph.D. student David Dickson examined male subjects of both mice and humans with traumatic experiences as closely related as possible between the two species. For the mice, the team exposed a select number of them to adolescent chronic social instability (CSI) stress, which included changing the cage composition of mice two times a week for 7 weeks beginning during adolescence.
This form of stress is known to enhance sociability defects and anxiety in offspring—particularly female offspring from the male’s lineage for generations. Sperm samples were acquired from the mice after the period of stress and were examined for a variety of RNA types, including miRNA.
For the human subjects, the team examined males who had suffered a significant stress early on in their lives such as sexual, verbal or physical abuse, and physical or emotional neglect. They employed the Adverse Childhood Experiences (ACE) questionnaire, which includes 10 yes or no questions about one’s experiences for the first 18 years of the individual’s life. Four or more “yes” answers puts the individual at a significantly higher risk to develop physical or mental health problems in the future.
The researchers examined miRNA in sperm samples submitted by 28 Caucasian male volunteers who completed the ACE questionnaire. Sperm samples were chosen from individuals with the 5 highest ACE scores (a score of 4 or higher) and 5 lowest scores (0-1).
The team discovered that the expression of miRNA-34 and miRNA-449, which have been known to work in tandem to develop the brain and sperm in mice, was reduced in both the mice and human males, inferring that future generations may be epigenetically predisposed to psychiatric issues. In the humans, expression of the two miRNAs was found to be inversely proportional to the men’s ACE scores: men with the more pervasive history of abuse displayed extreme reduction in expression of these 2 miRNAs when compared to the men who’ve suffered the least abuse.
David Dickson hopes that the crucial evidence gathered in this study can open up windows of opportunity to help discover a way to reverse the decreased expression of these two essential microRNAs, “Looking to the future, we may be able to figure out a way to restore the low miRNA levels found in men exposed to extreme trauma, because epigenetic changes, such as stress-induced decreases in sperm miRNA expression, are reversible, unlike genetic changes that alter the DNA sequence”.
Fieg adds that because abuse or dysfunctional family life is, unfortunately, more common these days, future studies would benefit by having physicians gather information from their patients regarding early life traumas and supplementing that with the correlation between PTSD and ACE scores and the data collected in this study. He also highlights that because the sensitive nature of the ACE questionnaire, an individual could feel embarrassed and withhold important information, so the discovery of these epigenetic markers on people affected by early traumas may assist future preventative medicine.
Fieg and Dickson look to increase the sample size in the future to dive deeper into the correlation between ACE scores and the expression of miRNA. They hope to measure the content of miRNA in subjects’ sperm over the course of their lives to determine the effect of early trauma on miRNA health and hope to develop a preventative action to halt and reverse the damage that stress causes to miRNA.
If you or somebody you know has suffered any sort of domestic abuse, you can find help at http://www.thehotline.org/.
Source: Feig, L. A. (2018). Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress. Translational Psychiatry, 8:101.
Reference: Tufts University Health Sciences Campus, Early life trauma in men associated with reduced levels of sperm microRNAs. Tufts Now. 22 May 2018. Web.