Advanced paternal age diversifies individual trajectories of vocalization patterns in neonatal mice

Summary Infant crying is an innate communicative behavior that is frequently impaired in certain neurodevelopmental disorders (NDDs). Since advanced paternal age is a reported risk factor for NDDs in offspring, we evaluated the impact of a father’s age on early vocal development in C57BL/6J mice. We recorded and applied a unique combination of computational analyses to ultrasonic vocalizations (USVs) emitted by mouse pups sired by young and aged fathers. Our data showed that advanced paternal age reduced the number and duration of USVs, and altered the syllable composition in pups. Moreover, pups born to young fathers showed convergent vocal characteristics with a rich repertoire during postnatal development, while those born to aged fathers exhibited more divergent vocal patterns with limited repertoire. Principal component analysis in conjunction with clustering analysis demonstrated that pups from aged fathers deviated from typical trajectories of vocal development, which were considered as atypical individuals. Thus, our study indicates that advanced paternal age has a significant effect on offspring’s early vocal development. It is suggested that the trajectories of vocal development could be a useful marker of the NDD-like phenotype associated with the advanced paternal age. In addition, our comprehensive computational analysis described here is an effective approach to characterize the altered individual diversity relevant to neurodevelopmental disorders. One Sentence Summary Advanced paternal age affects vocal development in early postnatal mice, with more pups showing atypical developmental trajectories.