Paternal immune activation by Poly I:C modulates sperm noncoding RNA profiles and causes transgenerational changes in
Elizabeth A Kleeman1, Sonali N Reisinger1, Pranav Adithya1
1Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
Brain, Behavior, and Immunity
|October 11, 2023
Summary
Paternal exposure to viral immune activation can alter offspring behavior and brain function across generations. This may be due to changes in sperm small noncoding RNA content, impacting intergenerational and transgenerational effects.
Area of Science:
- Neuroscience
- Epigenetics
- Reproductive Biology
Background:
- Paternal environmental factors can epigenetically influence offspring phenotypes.
- Maternal immune activation during gestation affects offspring neurodevelopment.
- The impact of paternal pre-conceptual immune activation on offspring is unknown.
Purpose of the Study:
- To investigate the effects of paternal pre-conceptual viral-like immune activation on F1 and F2 offspring behavior and physiology.
- To explore potential epigenetic mechanisms mediated by sperm small noncoding RNAs.
Main Methods:
- Mice fathers were injected with polyinosinic:polycytidylic acid (Poly I:C) or saline.
- Fathers were bred with control females four weeks post-injection.
- Offspring (F1 and F2) behavior, stress response, immune responsivity, and sperm small noncoding RNA profiles were analyzed.
Main Results:
- Poly I:C exposed fathers' F1 offspring exhibited depression-like behavior, altered stress responses, and hippocampal transcriptomic changes.
- F1 male offspring showed increased immune responsivity.
- F2 male offspring displayed altered anxiety-like behavior.
- Sperm microRNA and PIWI-interacting RNA content were significantly altered in Poly I:C treated males.
Conclusions:
- Paternal pre-conceptual viral immune challenge induces intergenerational and transgenerational effects on offspring brain and behavior.
- Alterations in sperm small noncoding RNA content may mediate these effects.
- This highlights a novel pathway for paternal environmental influence on offspring neurodevelopment.
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