The male offspring of calorie restricted fathers display reduced anxiety-like behavior as adults
In December 2015 Psychoneuroendocrinolog published an article called “Paternal calorie restriction prior to conception alters anxiety-like behavior of the adult rat progeny“. We asked one of the authors, Dr. Antonina Govic from RMIT University, to comment on this study.
Emerging evidence indicates that the environment of males before conception can have a profound impact on future generations. Whilst maternal experiences of stressors such as calorie restriction (CR) and corticosterone elevation are known to influence offspring stress-related behavior and physiology, little is known regarding the consequence to offspring of paternal exposure to these factors. Consequently, the aim of this study was to determine whether CR or corticosterone elevation of the male prior to conception would affect the behavioral and endocrine profile of the first generation male offspring. To investigate this, we exposed rats to calorie restriction (25% reduction in food) and corticosterone supplementation(200 µg/ml in drinking water) for approximately 6 weeks prior to mating. As expected, males exposed to CR exhibited a reduction in weight gain and decreased anxiety-like behavior.
Importantly, the adult offspring sired by CR males also exhibited a reduction in weight gain, food intake and serum leptin concentration compared to control sired offspring, indicating wide-reaching effects of paternal CR to appetite and metabolism. Moreover, CR offspring demonstrated reduced anxiety-like behavior in a number of rodent tests of anxiety. Offspring of males given the stress hormone corticosterone failed to show differences from controls. Collectively, these finding suggests a phenotypic transmission of the dietary environment from fathers to the progeny. This transmission could potentially be mediated epigenetically through modifications to the paternal germ cell.
The dietary experiences of the female during the perinatal period have been well and long established to affect the health, physiology and behavior of offspring throughout life. Interestingly, these effects have been observed to be present in a number of generations, indicating transgenerational effects of maternal diet. These effects are thought to be mediated epigenetically and the recent identification of various epigenetic mechanisms has further implicated a role for the transgenerational inheritance of phenotype by maternal nutritional status. Epigenetic control is thought to regulate gene expression, and thus various types of phenotypes (such as behavior, physiology, metabolism etc), by mechanisms that do not alter the DNA sequence. The role of the paternal dietary environment in offspring phenotype has not been examined to the degree maternal dietary experiences have. Studies examining archival data of famine exposed regions have certainly indicated a role for paternal diet in modifying the health of decedents. It is this; coupled with the increasing knowledge gleaned of epigenetics in transgenerational inheritance, that has motivated us to conduct this study.
Our findings demonstrate that the paternal dietary environment can influence the behavior and physiology of the offspring. These findings generate a number of avenues for future research. Namely there is a need to:
1) Characterize changes in gene expression: we know that paternal CR affects offspring behavior, physiology and endocrine systems, however, it is unclear which genes and how gene expression is altered by paternal CR.
2) Determine whether paternal dietary experiences are transgenerational: whilst we have demonstrated intergenerational inheritance effects of paternal diet, we need to examine subsequent generations to determine if these alterations are transgenerational and if so, how many generations express these phenotypes.
3) Identify the epigenetic mechanisms responsible for this effect: At this stage we do not know how information about the dietary conditions of the environment is transmitted through the male germ cell. It is unclear whether epigenetic processes such as DNA methylation, histone modifications and/or coding/noncoding RNAs are involved in this effect.
It will take time and ample research to determine the answers to these questions. Despite this, research into this area has profound implications for human health and functioning and well worth the effort.
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