Poster Presentation 44th Lorne Genome Conference 2023

Whole genome Nanopore DNA sequencing shows that chronic corticosterone supplementation in mice results in altered sperm DNA methylation in exposed animals and their offspring. (#249)

Coralina Collar Fernandez 1 , Terence Pang 1 , Quentin Gouil 2 , Ricardo de Paoli 3 , Yair Prawer 3 , Rebekah Harris 1 , Lucas B Hoffmann 1 , Josie Gleeson 3 , Michael B Clak 3 , Anthony Hannan 1
  1. Epigenetics and neural plasticity, Florey institute of Neuroscience and mental health. University of Melbourne, Melbourne, Victoria, Australia
  2. Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  3. Anatomy and Physiology, , The University of Melbourne, Melbourne, Victoria, Australia

Stress and trauma have been shown to have effects that persist across multiple generations. Our lab uses a mouse model of corticosterone (CORT) supplementation to model HPA-axis activation during periods of chronic stress. We previously reported on the transgenerational molecular and behavioural effects in this model 1. In this study we sequenced mouse sperm DNA of CORT exposed fathers (F0) and their offspring (F1) using Oxford Nanopore Technologies (ONT) long-read sequencing,  which allowed us to characterise the methylation (mC) status of more than 18 million CpG in the genome. This technique was performed without bisulphite conversion or PCR, thus avoiding amplification and conversion bias. Moreover, ONT also allowed us to determine the state of hydroxy methylation (hmC) from the same sequencing data. Analysis of differentially methylated regions (DMRs) revealed that CORT supplementation led to decreased mC at specific regions and increased hmC. Moreover, sperm DNA of F1 offspring were found to also have decreased mC and increased  hmC, but in different genomic regions to CORT-treated mice. In conclusion, we showed that chronic elevation of corticosterone in mice altered sperm DNA methylation in both F0 and F1 mice. Yet, F0 sperm methylation changes are not inherited, a different set of DMRs were identified in F1 sperm. How sperm DNA methylation changes may contribute to transgenerational epigenetic inheritance remains unclear and  requires further investigation.

  1. Short, A. K., Fennell, K. A., Perreau, V. M., Fox, A., O’Bryan, M. K., Kim, J. H., Bredy, T. W., Pang, T. Y., & Hannan, A. J. (2016). Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Translational Psychiatry, 6(6), e837–e837. https://doi.org/10.1038/tp.2016.109