Separating the effects of sex hormones and sex chromosomes on behavior in the African pygmy mouse Mus minutoides, a species with XY female sex reversal

In mammals, most sex differences in phenotype are controlled by gonadal hormones, but recent work on transgenic mice have shown that sex chromosomes can have a direct influence on sex-specific behaviors. In this study, we take advantage of the naturally occurring sex reversal in a mouse species, Mus minutoides , to investigate for the first time the relationship between sex chromosomes, hormones and behaviors in a wild species. In this model, a feminizing variant of the X chromosome, named X*, produces three types of females with different sex chromosome complements (XX, XX*, and X*Y), associated with alternative behavioral phenotypes, while all males are XY. We thus compared the levels of three major circulating steroid hormones (testosterone, corticosterone and estradiol) in the four sex genotypes to disentangle the influence of sex chromosomes and sex hormones on behavior. First, we did not find any difference in testosterone levels in the three female genotypes, although X*Y females are notoriously more aggressive. Second, in agreement with their lower anxiety-related behaviors, X*Y females and XY males display lower baseline corticosterone concentration than XX and XX* females. Instead of a direct hormonal influence, this result rather suggests that sex chromosomes may have an impact on the baseline corticosterone level, which in turn may influence behaviors. Third, estradiol concentrations do not explain the enhanced reproductive performance and maternal care behavior of the X*Y females compared to the XX and XX* females. Overall, this study highlights that most of the behaviors varying along with sex chromosome complement of this species are driven by genetic factors rather than steroid hormone concentrations. ### Competing Interest Statement The authors have declared no competing interest.