Delayed Fatherhood in Mice Decreases Reproductive Fitness and Longevity of Offspring1

Abstract

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.

Parental age at childbirth and age of menarche in the offspring

“…Animal studies suggest that advanced parental age may reduce reproductive fitness and fecundity in female offspring (Tarin et al, 2003;Garcia-Palomares et al, 2009). These findings suggest that there may be a moderate association between parental age and timing of menarche as well.…”

“…Advanced maternal age at childbirth has been linked to menstrual disorders and subfecundity in daughters owing to endocrinological irregularities (Smits et al, 1997). Studies on mice have shown that delayed parenthood, both maternal and paternal, reduces reproductive fitness, particularly among female offspring (Tarin et al, 2003;Garcia-Palomares et al, 2009).…”

Transgenerational interactions involving parental age and immune status affect female reproductive success inDrosophila melanogaster

“…Recently, however, and contrary to traditional belief, research has emerged to show that general paternal effects can affect a number of life-history traits in the offspring [4,6], and that these effects may also be sensitive to age-related senescence in fathers [6]. For example, studies have associated older fathers with the frequency of birth defects in humans [57], with reduced reproduction and longevity in laboratory mice (Mus musculus) [58], and with reduced fertility, offspring weight and increased offspring mortality in brown Norway rats (Rattus norvegicus) [59]. Paternal age effects have also been recorded in insects; old fathers have been noted to produce longer-lived offspring in D. melanogaster [52], and older fathers exhibited lower reproductive output when exposed to metabolic stress in the butterfly Pieris brassicae [20].…”

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.…”