Aberrant anogenital distance in XXSxv (‘sex‐reversed’) pseudomale mice

Abstract

Anogenital distance (AGD). a sex differentiation marker in mice (Mus musculus), is thought to be a secondary sexual trait exclusively regulated by androgens during development. However, recent studies suggest that some so‐called secondary sexual traits may be influenced by sex‐chromosomal genotype. To explore this question further we studied the AGD of the XXSxr 'sex‐reversed’mouse, which has adequate androgens for masculinization.The AGDs of adult and prepubertal XY, XYSxr carrier, XXSxr 'sex‐reversed’and XX mice were measured. We found that adult XXSxr 'sex‐reversed’mice (which we refer to as pseudomales) and XYSxr carriers have shorter mean AGDs than their XY siblings. Prepubertal XXSxr animals also have shorter mean AGDs than their XY siblings when AGD is expressed as a proportion of body length. XX adult and prepubertal mice have significantly shorter AGDs than the other genotypes at similar stages of development. The differences in AGD between adult and prepubertal XY and XXSxr sibs, and adult XY and XYSxr sibs, reported here, do not appear to be due to androgen levels, since adult testicular and serum testosterone levels are higher in pseudomales and carriers than in XY mice, and fetal pseudomale androgen levels also appear to be at least as high as those of normal males. Furthermore, the AGD differences between genotypes are not correlated to differences in testis size. We conclude that the differences are likely to be due to a tissue specific effect of the genetic constitution of the individuals, as is the case with scrotal development in the marsupial Macropus eugenii (the tammar wallaby).