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How do paternal experiences impact offspring behaviour, physiology and reproductive fitness?

Issues with a child's health have historically been linked to maternal factors, such as her health status before conception and throughout pregnancy. In the past decade, emerging evidence indicates that the father's health is equally essential. My research is a unique combination of neuroscience and reproductive biology.  I discovered that stress changes the molecular profile of sperm and that paternal stress alone can be linked to anxiety disorders in his sons. I am now working to decipher the mechanisms involved in this indirect relationship.

Aims

To discover how physical and environmental stressors impacting an individual lead to transgenerational shifts in brain development, anxiety behaviour, stress-response, metabolism and fertility of subsequent generations.  

It is estimated that 10% of the population will experience PTSD at least once in their lifetime, and animal model studies suggest that paternal traumatic stress is linked to behavioural shifts and potential learning difficulties in their offspring. 

The 2015 Australian Psychological Society Stress & Well-being survey reported that ~50% of us experience moderate levels of stress, with young adults are particularly vulnerable. Our lab developed a unique approach to model chronic low-level stress in young adult male mice (Short et al., Transl Psychiatry 2016) and we discovered the emergence of anxiety behaviours in the male offspring and subsequent behavioural alterations in the grand-offspring. We recently found that the F1 offspring are also hypersensitive to antidepressant treatment (Rawat et al., Environ Epigenet 2018).  

This project has a broad scope to address multiple aspects of transgenerational research and offers students the opportunity to learn a range of research techniques. Rodent behavioural testing will be used to further characterise the behavioural phenotype associated with risk-aversion and anxiety. These are paired closely with physiological studies of stress-response using blood hormone assays and gene-expression profiling of dissected stress-regulating brain regions such as the hypothalamus and hippocampus. Characterisation of brain development and function will involve immunohistological studies of cell proliferation and turnover in the hippocampus (a key region for regulating cognition and emotion) and frontal cortex. Examinations of the male reproductive system will also be conducted to examine how environmental stressors alter the physical parameters of sperm maturation with implications for male subfertility.

Students have to be able to work as part of a team, and will gain experience in a range of techniques including animal behavioural testing, brain and organ dissections, RNA/DNA expression analyses, cell turnover and stress-related hormone assays.

Stress-associated transgenerational effects involve a change in sperm microRNA profile. The HPA axis involves glucocorticoid regulation of stress response. The glucocorticoid receptor is also highly expressed in the testes and epididymis, and triggers exocytosis of small-RNA containing exosomes ‘epididymosomes’. These fuse with sperm to confer different stress-specific microRNA profiles.

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