Evaluating the roles of testosterone and sex-linked genes in territorial aggression of sex-reversed XY females in the African pygmy mouse

Sex differences in social aggression are widespread across the animal kingdom, with males typically displaying greater territoriality. While this dimorphism has traditionally been attributed to sex hormones, sex chromosomes can also contribute to it independently of hormonal influence. In the African pygmy mouse Mus minutoides, naturally occurring sex-reversed XY females (named X*Y due to a mutation on the X chromosome) are highly territorial in comparison to the other female genotypes present in the population (XX and XX*). However, the molecular basis of this phenotype remains unknown. Here, we evaluate molecular factors - known to correlate with aggressiveness - following a standardized behavioural assessment of aggression. We focus on i) the androgen pathway by quantifying testosterone serum levels and expression of its receptor in the brain; ii) the brain dopaminergic system through expression of dopamine-regulating genes, including the sex-determining Sry gene; and iii) neuroendocrine circuits, via vasopressin and oxytocin expression. These systems, although distinct, converge on hypothalamic-limbic circuits that regulate social behaviour and threat responses, providing an integrated framework for the modulation of aggression. Contrary to earlier reports, we found reduced level of aggression in X*Y females, likely to reflect a breeding facility effect. We also observe no correlations between aggressiveness and androgen levels or gene expression of the tested factors. However, our results support a stimulation of the dopaminergic system and of the oxytocin pathway following the agonistic assay suggesting their potential involvement in aggression-related responses. This further supports the idea that aggression is multifactorial. It is shaped by the interaction of several neuroendocrine and neurotransmitter pathways rather than a single determinant.