Paternal transmission of behavioural and metabolic traits induced by postnatal stress to the 5thgeneration in mice

ABSTRACT Life experiences and environmental conditions in childhood can change the physiology and behaviour of exposed individuals and in some cases, of their offspring. In rodent models, stress/trauma, poor diet and endocrine disruptors in a parent have been shown to cause phenotypes in the direct progeny, suggesting intergenerational inheritance. A few models also examined transmission to further offspring and suggested transgenerational inheritance, but such multi-generations inheritance is not well characterized. Our previous work in a mouse model of early postnatal stress showed that behaviour and metabolism are altered in the offspring of exposed males up to the 4 th generation in the patriline and up to the 2 nd generation in the matriline. The present study examined if in the patriline, symptoms can be transmitted beyond the 4 th generation. Analyses of the 5 th and 6 th generation of mice revealed that altered risk-taking and glucose regulation caused by postnatal stress are still manifested in the 5 th generation but are attenuated in the 6 th generation. Some of the symptoms are expressed in both males and females, but some are sex-dependent and sometimes opposite. These results indicate that postnatal trauma can affect behaviour and metabolism over many generations, suggesting epigenetic mechanisms of transmission.