Pathogenic Infection in Male Mice Changes Sperm Small RNA Profiles and Transgenerationally Alters Offspring Behavior

Shiraz Tyebji; Anthony J Hannan; Christopher J Tonkin

doi:10.1016/j.celrep.2020.107573

Pathogenic Infection in Male Mice Changes Sperm Small RNA Profiles and Transgenerationally Alters Offspring Behavior

Cell Rep. 2020 Apr 28;31(4):107573. doi: 10.1016/j.celrep.2020.107573.

Authors

Shiraz Tyebji¹, Anthony J Hannan², Christopher J Tonkin³

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, VIC, Australia.
² Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, VIC, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Parkville 3052, VIC, Australia.
³ The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, VIC, Australia. Electronic address: tonkin@wehi.edu.au.

PMID: 32348768
DOI: 10.1016/j.celrep.2020.107573

Abstract

Germline epigenetic factors influence transgenerational inheritance of behavioral traits upon changes in experience and environment. Immune activation due to infection can also modulate brain function, but whether this experience can be passed down to offspring remains unknown. Here, we show that infection of the male lineage with the common human parasite Toxoplasma results in transgenerational behavioral changes in offspring in a sex-dependent manner. Small RNA sequencing of sperm reveals significant transcriptional differences of infected animals compared to controls. Zygote microinjection of total small RNA from sperm of infected mice partially recapitulates the behavioral phenotype of naturally born offspring, suggesting an epigenetic mechanism of behavioral inheritance in the first generation. Our results demonstrate that sperm epigenetic factors can contribute to intergenerational inheritance of behavioral changes after pathogenic infection, which could have major public health implications.

Keywords: Toxoplasma gondii; cognitive changes; epigenetics; small RNA; transgenerational.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Behavior, Animal / physiology*
Disease Models, Animal
Epigenomics / methods*
Infections / complications*
Male
Mice
RNA / metabolism*
Spermatozoa / metabolism*
Toxoplasmosis / physiopathology*

Substances

RNA