Mimicking bacterial infection in male mice changes sperm small RNA profiles and multigenerationally alters offspring behavior and physiology.

Autor: Liao H; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia. Electronic address: huan.liao@florey.edu.au., Lu D; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Reisinger SN; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Kleeman EA; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., van de Garde N; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Gubert C; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia., Hannan AJ; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: anthony.hannan@florey.edu.au.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Jul; Vol. 119, pp. 520-538. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.bbi.2024.04.017
Abstrakt: Paternal pre-conceptual exposures, including stress, diet, substance abuse, parasite infection, and viral immune activation via Poly I:C, have been reported to influence the brains and behavior of offspring through sperm epigenetic changes. However, the effects of paternal (F0) pre-conceptual exposure to bacterial-induced immune activation on the behavior and physiology of F1 and F2 generations remain unexplored. We examined this using C57BL/6J mice. Eight-week-old males (F0) received a single intraperitoneal injection of the bacterial mimetic lipopolysaccharide (LPS: 5 mg/kg) or 0.9 % saline (vehicle control) before mating with naïve females at four weeks post-injection. Comprehensive behavioral assessments were conducted to investigate anxiety, social behaviors, depressive-like behaviors and cognition in both the F1 and F2 generations within the age range of 8 to 14 weeks. Results demonstrated that only female offspring of LPS-exposed fathers exhibited reduced anxiety levels in the light/dark box, large open field, and novelty-suppressed feeding test. These F1 female offspring also exhibited heightened sociability in the 3-chambered social interaction test and a reduced preference for saccharin in the saccharin preference test. Additionally, the F1 male offspring of LPS-challenged males demonstrated an increased total distance traveled in the light/dark box and a longer distance covered in the light zone. They also exhibited diminished preference for social novelty in the 3-chambered social interaction test and an elevated novel arm preference index in the Y-maze. In the F2 generation, male descendants of LPS-treated fathers showed reduced latency to feed in the novelty-suppressed feeding test. Additionally, the F2 generation of LPS-challenged fathers, but not the F1 generation, displayed enhanced immune response in both sexes after an acute LPS immune challenge (5 mg/kg). Analysis of sperm small noncoding RNA profiles from LPS-treated F0 mice revealed significant changes at 4 weeks after administration of LPS. These changes included three microRNAs, eight PIWI-interacting RNAs, and two transfer RNAs, exhibiting significant upregulation (mmu-miR-146a-5p, mmu-piR-27082 and mmu-piR-29102) or downregulation (mmu-miR-5110, mmu-miR-467e-3p, mmu-piR-22583, mmu-piR-23548, mmu-piR-36341, mmu-piR-50293, mmu-piR-16583, mmu-piR-36507, Mus_musculus_tRNA-Ile-AAT-2-1 and Mus_musculus_tRNA-Tyr-GTA-1-1). Additionally, we detected 52 upregulated small noncoding RNAs (including 9 miRNAs, 41 piRNAs, and 2 tRNAs) and 7 downregulated small noncoding RNAs (3 miRNAs, 3 piRNAs, and 1 tRNA) in the sperm of F1 offspring from LPS-treated males. These findings provide compelling evidence for the involvement of epigenetic mechanisms in the modulation of brain function and immunity, and associated behavioral and immunological traits, across generations, in response to bacterial infection.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: