Delayed Fatherhood in Mice Decreases Reproductive Fitness and Longevity of Offspring

This study aims to analyze, in mice, the long-term effects of delayed fatherhood on reproductive fitness and longevity 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 reproductive fitness of first-generation (F-1) females was tested from the age of 25 wk until the end of their reproductive life. In F-1 males, the testing period ranged from the age of 52 wk until death. Breeding F-1 females from the 120-wk group displayed interbirth intervals longer than females from the 12-, 70-, and 100-wk groups. Furthermore, F-2 pups begotten by F-1 studs exhibited weaning weights lower than pups from the 12- and 70-wk groups. Offspring from the 120-wk group exhibited shorter survival times associated with lower incidence of tumorigenesis and higher loss of body weight when approaching death when compared to F-1 offspring from younger age-groups. The results indicate that advanced paternal age at conception has negative long-term effects on reproductive fitness and longevity of offspring in the mouse model.