Mother's Prior Intrauterine Position Affects the Sex Ratio of Her Offspring in House Mice

Sex ratio alterations related to environmental factors occur in several mammals, but no mechanism has been identified to explain the adjustment. Intrauterine position (IUP) may provide the context in which such alterations occur. Previous studies on house mice and gerbils reveal that the position of a fetus in the uterus in relation to the sex of its neighbors influences its later anatomy, physiology, and behavior. The anogenital distance (AGD) of females located between two males (2M) is longer than that of females not between two males (OM). We have found that the IUP, as determined by cesarean section and by an index of the AGD, correlates with the sex ratio of the litters produced by female mice. The sex ratio of the first litter born to 2M females was 58% males, for 1M females was 51% males and for OM females was 42% males. The effect on sex ratio continues into the second litter. The number of pups produced by mothers of different IUPs in her first two litters did not differ, suggesting that the sex ratio adjustment occurs prior to parturition. These results provide a basis for the natural variability observed in sex ratios of litter-bearing mammals and suggest that one or more intrauterine mechanisms may be responsible for environmentally related sex ratio alterations.