Sex differences in juvenile mouse social behavior are influenced by sex chromosomes and social context

Abstract

Play behavior in juvenile primates, rats and other species is sexually dimorphic, with males showing more play than females. In mice, sex differences in juvenile play have only been examined in out-bred CD-1 mice. In this strain, contrary to other animals, male mice display less play soliciting than females. Using an established same-sex dyadic interaction test, we examined play in in-bred C57BL/6J (B6) 21-day-old mice. When paired with non-siblings, males tended to be more social than females, spending more time exploring the test cage. Females displayed significantly more anogenital sniffing and solicited play more frequently than did males. To determine if the origin of the sex difference was sex chromosome genes or gonadal sex, next we used the four core genotype mouse. We found significant interactions between gonadal sex and genotype for several behaviors. Finally, we asked if sibling pairs (as compared to non-siblings) would display qualitatively or quantitatively different behavior. In fact, XX females paired with a sibling were more social and less exploratory or investigative, whereas XY males exhibited less investigative and play soliciting behaviors in tests with siblings. Many neurobehavioral disorders, like autism spectrum disorder (ASD), are sexually dimorphic in incidence and patients interact less than normal with other children. Our results suggest that sex chromosome genes interact with gonadal hormones to shape the development of juvenile social behavior, and that social context can drastically alter sex differences. These data may have relevance for understanding the etiology of sexually dimorphic disorders such as ASD.

Figure 1

Mean +/− SEM time (in seconds) spent engaged in social and nonsocial behaviors during the last 20 minutes of a 30-minute test. Panels a) and b) Data from Experiment 1: social tests with non-sibling partners B6 pairs (n=8 females, 10 males). Panels c) and d) Data from Experiment 2: social tests with non-sibling partners, FCG pairs (n=10–12 per group). Panels e) and f) Data from Experiment 3: social tests with sibling partners, FCG pairs (n=10–12 per group). * Significantly different from males, p<0.01. ** Significantly different from XY females and XX males, p<0.02 or less. *** Significantly different from all other groups, p< 0.03. F=female, M=male, B6=C57BL/6J, FCG= four core genotypes.

Figure 2

Mean +/− SEM number of investigative or play soliciting behaviors during the last 20 minutes of a 30-minute test. Panels a) and b) Data from Experiment 1: social tests with non-sibling partners, B6 pairs (n=8 females, 10 males). Panels c) and d) Data from Experiment 2: social tests with non-sibling partners, FCG pairs (n=10–12 per group). Panels e) and f) Data from Experiment 3: social tests with sibling partners, FCG pairs (n=10–12 per group). ^ Females tend to display more investigations than males, p=0.059. * Significantly different from males, p<0.02. ** Significantly different from XY females and XX males, p<0.02 or less. *** Significantly different from XX females and XY males, p<0.004. F=female, M=male, B6=C57BL/6J, FCG= four core genotypes.