The anogenital distance index, a predictor of the intrauterine position effects on reproduction in female house mice.

The anogenital distances (AGD) of newborn female house mice vary as a function of prior intrauterine position. Females with long AGDs are more likely to be derived from intrauterine positions adjacent to males (2M) than females not adjacent to males (0M). Females with a male on one side (1M) show intermediate AGDs. Hence the AGD reflects the degree of androgenization experienced by the female in utero and correlates with a number of androgen-dependent anatomical, physiological, and behavioral events in adulthood. This experiment tested the usefulness of AGD measurements of female house mice taken at weaning rather than at birth as an index of prior androgenization. The AGD was normalized for body weight at weaning to yield an anogenital distance index (AGDI). Intrauterine position (IUP) was determined by caesarian section. Pups were marked and reared by foster mothers. Comparison of AGDI showed that 0M females had a significantly lower mean AGDI score than 2M females and 1M females were intermediate. This confirmed that AGDI reflects prior IUP and can be used as an index of prenatal androgenization. While testing for responsiveness to male urine, a stimulus known to accelerate puberty, only females from the 1M and 2M positions differed from controls indicating that 0M females had already attained puberty. Choosing females from unknown IUPs with short-AGDIs, mid-AGDIs, and long AGDIs and treating them with either urine or saline on the nose for the 4 days after weaning yielded much the same response indicating that AGDI can also be used to preselect females for sensitivity to factors influencing puberty. These results demonstrate that some of the variability known to be related to intrauterine position can be predicted by AGDI, a relatively easy measure to acquire at weaning in commonly used laboratory rodents. Such preselection could reduce variability of experimental results in the conduct of studies related to rodent reproduction and may reduce the number of animals needed without loss of predictive ability.

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.