Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/121091
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Type: | Journal article |
Title: | Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. |
Author: | Short, A. Fennell, K. Perreau, V. Fox, A. O'Bryan, M. Kim, J. Bredy, T. Pang, T. Hannan, A. |
Citation: | Translational Psychiatry, 2016; 6(6):e837-e837 |
Publisher: | Nature |
Issue Date: | 2016 |
ISSN: | 2158-3188 2158-3188 |
Statement of Responsibility: | A.K. Short, K.A. Fennell, V.M. Perreau1, A. Fox, M.K. O’Bryan, J.H. Kim, T.W. Bredy, T.Y. Pang and A.J. Hannan |
Abstract: | Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic-pituitary-adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light-dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of paternal stress-induced traits across generations in a process involving small noncoding RNA signals transmitted by the male germline. |
Keywords: | Spermatozoa Pituitary-Adrenal System Hypothalamo-Hypophyseal System Animals Mice, Inbred C57BL Corticosterone Brain-Derived Neurotrophic Factor Insulin-Like Growth Factor II MicroRNAs Depression Anxiety Fear Maze Learning Paternal Exposure Sex Factors Gene Expression Pregnancy Phenotype Exons Female Male RNA, Small Untranslated |
Rights: | © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/ |
DOI: | 10.1038/tp.2016.109 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1083468 http://purl.org/au-research/grants/arc/FT100100835 |
Published version: | http://dx.doi.org/10.1038/tp.2016.109 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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