RT Journal Article
SR Electronic
T1 Paternal Stress Exposure Alters Sperm MicroRNA Content and Reprograms Offspring HPA Stress Axis Regulation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9003
OP 9012
DO 10.1523/JNEUROSCI.0914-13.2013
VO 33
IS 21
A1 Ali B. Rodgers
A1 Christopher P. Morgan
A1 Stefanie L. Bronson
A1 Sonia Revello
A1 Tracy L. Bale
YR 2013
UL http://www.jneurosci.org/content/33/21/9003.abstract
AB Neuropsychiatric disease frequently presents with an underlying hyporeactivity or hyperreactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic–pituitary–adrenal (HPA) axis dysregulation, we exposed mice to 6 weeks of chronic stress before breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA stress axis responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis, revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm microRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk.