By Nick Bitterlich
Imitation is a crucial component of brain development in children, who pick up habits from their parents starting at an early age. The influence of biological parents transgresses behavioural patterns that are mirrored by their offspring. Lifestyle habits can imprint or encode heritable phenotype changes that do not involve alterations in the DNA sequence. Daily habits exhibited by parents, such as regular exercise and a balanced diet have positive effects on the transmission of genetic code.
The intergenerational inheritance of exercise-induced traits has been suggested to have a beneficial impact on offspring cognition, neurogenesis, and mitochondrial health. One study compared the progeny of sedentary and active mice to determine the extent to which future generations are influenced by those they succeed (McGreevy et al., 2019). An enhancement of germline fitness was suggested by increased mitochondrial citrate synthase, a key enzyme involved in the Claisen condensation where it promotes the production of CoA and citrate. These metabolites serve important regulatory functions in the body, with citrate preventing Ca2+ from interacting with the coagulation system and thus inhibiting clotting and ensuring longevity (Palta et al., 2014). Increased mitochondrial activity and functionality also has positive effects on dendritogenesis and cell differentiation of nascent neurons. Similarly, previous results suggest the structure and function of the hippocampus, the region of the brain responsible for memory and learning, is modified in individuals that participate in regular physical exertion (Cooper et al, 2017). The associated boost in neurogenesis and synaptic plasticity influence information processing function of synapses that can adapt to changing demands of the environment, a selective advantage to individuals with high plasticity.
Reports have revealed positive effects on long term potentiation of the hippocampus through male sperm RNA. GSEA studies discovered an enrichment of microRNA activity in the progeny of male parents subjected to physical exercise (McGreevy et al, 2019). Many of the genes that are regulated by the inhibitory effects of microRNA activity show the tendency to be either over or under-expressed in exercised fathers compared to those with a sedentary lifestyle. In particular, the upregulation of miR212/132 in oocytes increases the gene transcription in the hippocampus and enhances synaptic plasticity (Wanet et al, 2012).
Drosophila studies have identified dietary influences on progeny health in several subsequent generations. Flies that were subjected to low protein/high sucrose diets had an influx of cellular glycogen with females laying fewer eggs (Moraes, 2014). These changes also altered offspring reproduction patterns in conjunction with increased body weight, which resulted in repercussions in numerous cellular processes including cell proliferation and courtship. In a similar study, the offspring of males with a high sucrose diet appeared to be pre-sensitized to an obesogenic diet (Brookheart and Duncan, 2017). This was suggested by an overall increase in body weight and TAG lipid droplet size. At normal levels, the latter is a central regulator of lipid uptake, metabolism, trafficking but with overexpression, the risk of obesity-associated disease increases significantly (Musselman and Kühnlein, 2018). Although the effects of diet are central in the health status of drosophila progeny, the mechanism by which these changes are inherited remains to be understood.
In the same nature that exercise can have a beneficial effect on offspring, nicotine exposure of parental generation males can result in hyperactive and attention deficit male progeny. These nicotine exposed males showed impairment of dopamine neurotransmitters and receptors via methylation of the associated gene promoter regions, accelerating the formation of neurodevelopmental disorders. This was observed in following generations as well. The phenotypes observed in test mice aligned with observations associated with ADHD and autism in humans, suggesting cigarette consumption (and the associated nicotine exposure) may induce neurobehavioral impairments in descendants (McCarthy et al., 2018). This should open up discussion on tobacco usage and call attention to the need to revisit public policy.
Real-life examples of epigenetic changes passed on to progeny are plentiful. Mice that received shocks after smelling sweet almonds began to fear this specific smell. Their progeny and 2 subsequent generations followed this pattern, the result of modified M71 glomeruli (Dias & Ressler, 2014). During the hunger winter in 1945, the west of the Netherlands suffered from an extreme lack of food. Children conceived from parents that endured the famine had fewer methyl groups on the insulin-like growth factor 2. The theory is that the metabolism of these children was set at an economical level to accommodate the shortage of resources when they were exposed to famine in the uterus of their mothers. Surprisingly, these children were initially smaller than their same-aged counterparts in other non-famine exposed nations, but later in life suffered from an increased risk of glucose intolerance, obesity and cardiovascular disease (Heijmans et al, 2018).
In a society with a prevalence of maternal and paternal obesity, there is an ever-increasing threat to the health of offspring and subsequent generations. Conscious diet, exercise and lifestyle choices made by parents can have potentially detrimental effects on progeny, that have no control over the inheritance of their genetic code. This emulates the immense importance of inducible epigenetic changes and the complexity of metabolic programming in the hands of parents.
References:
Brookheart, R.T. and Duncan, J.G. (2016). Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster. Reproduction, pp.R79–R90.
Cooper, C., Moon, H.Y. and van Praag, H. (2017). On the Run for Hippocampal Plasticity. Cold Spring Harbor Perspectives in Medicine, 8(4), p.a029736.
Dias, B.G. and Ressler, K.J. (2013). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience, [online] 17(1), pp.89–96. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923835/.
Heijmans, B.T., Tobi, E.W., Stein, A.D., Putter, H., Blauw, G.J., Susser, E.S., Slagboom, P.E. and Lumey, L.H. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings of the National Academy of Sciences, [online] 105(44), pp.17046–17049. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579375/.
McCarthy, D.M., Morgan, T.J., Lowe, S.E., Williamson, M.J., Spencer, T.J., Biederman, J. and Bhide, P.G. (2018). Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants. PLOS Biology, 16(10), p.e2006497.
McGreevy, K.R., Tezanos, P., Ferreiro-Villar, I., Pallé, A., Moreno-Serrano, M., Esteve-Codina, A., Lamas-Toranzo, I., Bermejo-Álvarez, P., Fernández-Punzano, J., Martín-Montalvo, A., Montalbán, R., Ferrón, S.R., Radford, E.J., Fontán-Lozano, Á. and Trejo, J.L. (2019). Intergenerational transmission of the positive effects of physical exercise on brain and cognition. Proceedings of the National Academy of Sciences, 116(20), pp.10103–10112.
Moraes, T.G.V. (2014). Effect of maternal dietary energy and protein on live performance and yield dynamics of broiler progeny from young breeders. Poultry Science, [online] 93(11), pp.2818–2826. Available at: https://www.sciencedirect.com/science/article/pii/S0032579119385335?via%3Dihub [Accessed 5 Feb. 2021].
Palta, S., Saroa, R. and Palta, A. (2014). Overview of the coagulation system. Indian Journal of Anaesthesia, [online] 58(5), p.515. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260295/.
Wanet, A., Tacheny, A., Arnould, T. and Renard, P. (2012). miR-212/132 expression and functions: within and beyond the neuronal compartment. Nucleic Acids Research, [online] 40(11), pp.4742–4753. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367188/.
Imperial Bioscience Review 