Prenatal effects on reproductive capacity during aging in female mice

The production of live young during successive pregnancies was investigated in female CF-1 house mice (Mus musculus) identified at cesarean delivery as having developed in utero between 2 male fetuses (2M females) or not next to a male fetus (0M females). 2M female mice have previously been found to be exposed to higher concentrations of testosterone than 0M females during fetal life, presumably as a result of the transport of steroids between contiguous fetuses. 0M and 2M females were paired with stud males. The males were removed prior to delivery of a litter and replaced by other males when the litter was weaned. This process was repeated until: 1) a female did not become pregnant within 2.5 mo or 2) two successive litters were produced in which all of the pups were dead. In Experiment 1 females were first mated when 25 days old, and 2M females ceased producing litters containing live pups at a younger age and after fewer litters than did 0M females; however, many females were terminated from the study as a result of producing 2 successive litters of dead young rather than failing to become pregnant during a 2.5-mo period. There was a gradual decline in the number of live young produced by 0M females as a function of age and parity, but 2M females abruptly ceased producing any live young after producing a litter of normal size. For the last live litter, there were thus significantly fewer live young produced by 0M females than by 2M females. None of these differences were observed in Experiment 2, in which 0M and 2M females were mated for the first time beginning at 7 mo of age. The 2M females in this experiment ceased producing live young at a significantly older age than did the 2M females first mated at puberty. In contrast, there was no effect of age at initial mating on the age at which 0M females ceased producing live young. This finding suggests that exposure of 2M females to elevated titers of testosterone during fetal life results in a reduction in reproductive life span if they first become pregnant during the pubertal period.