Long-Term Effects of Delayed Fatherhood in Mice on Postnatal Development and Behavioral Traits of Offspring1

Abstract

This study aims to analyze, in mice, the long-term effects of delayed fatherhood on postnatal development, spontaneous motor activity, and learning capacity of offspring. Hybrid parental-generation (F(0)) males, at the age of 12, 70, 100, and 120 wk, were individually housed with a randomly selected 12-wk-old hybrid female. The resulting first-generation (F(1)) offspring were tested for several developmental and behavioral variables. Cumulative percentage of F(1) pups that attained immediate righting in the 120-wk group was lower than that found in the 12-, 70-, and 100-wk groups. Furthermore, the postnatal day of attaining immediate righting was higher in pups from the 120-wk group when compared to pups from the other age-groups. At the age of 20 wk, F(1) offspring from the 120-wk group displayed lower counts of motor activity than offspring from the 12-, 70-, and 100-wk groups. One week later, a higher percentage of offspring from the 100- and 120-wk groups entered the dark compartment during the retention trial of the passive-avoidance test when compared to offspring from the 12-wk group. Offspring from the 120-wk group exhibited also lower step-through latency in the retention trial than offspring from the 12-, 70-, and 100-wk groups. These results show that advanced paternal age at conception has long-term effects on preweaning development, spontaneous motor activity, and reduced passive-avoidance learning capacity of mouse offspring.

Advancing parental age and autism: multifactorial pathways

“…Since then, most animal model work related to APA has been based on the mouse. A decrease in learning in the offspring of older sires aged 25-30 months was confirmed, as well as a decrease in motor activity in the offspring of 30 month old sires [20]. Behavioral and brain structural effects have been observed in the offspring of 'younger old' sires as well.…”

Paternal diet-induced obesity impairs embryo development and implantation in the mouse

“…This has been examined particularly for the female gametes, or developing embryo (34,38,39), with relatively few examples of paternal programming. However, delaying fatherhood (40)(41)(42)(43), paternal smoking (44,45), and paternal alcohol consumption (46,47) have all been linked to impaired offspring health and longevity. There is some evidence that parental obesity increases the risk of children becoming overweight or obese (48,49), and similarly our initial preliminary observations in the mouse suggest that offspring from obese fathers were heavier before weaning than those from lean fathers.…”

Paternal age and mental health of offspring

“…Another study comparably showed reduced capacity for passive-avoidance learning for offspring of older sires[41] and another found alterations in cortical growth, which are perhaps relevant to the behavioral findings[42]. Both schizophrenia and autism entail reduced learning ability, so these findings may be relevant to the mechanism linking later paternal age to these conditions[35, 43-45].…”