Oxytocin deficiency causes sex-dependent changes in medaka social familiarity and mate choice

Social recognition and flexible behavioral adaptation to social context are crucial for many animal species, and their disruption is implicated in neurodevelopmental disorders like autism spectrum disorder. Understanding the molecular underpinnings of these processes is vital. Oxytocin, a neuropeptide widely recognized for its role in social behavior, exhibits diverse and often sex-specific actions across species, making its precise regulatory mechanisms in complex social interactions, such as mate choice, poorly understood. This study addresses this gap by investigating how oxytocin influences familiarity-dependent mate selection.

Researchers utilized oxytocin-deficient medaka fish, a model organism relying heavily on visual cues for social recognition, to investigate its role in mate choice. Wild-type and oxytocin-deficient male and female medaka were observed in various social interaction paradigms, including dyadic (one male, one female) and triadic (one female, two males) setups, to assess familiarity-dependent mate acceptance, courtship frequency, and mate-guarding behavior. Additionally, whole-brain transcriptome analyses were performed on both sexes to identify molecular pathways altered by oxytocin deficiency, and a novel UPA-seq method was introduced for future RNA-protein interaction studies.

Oxytocin deficiency profoundly altered familiarity-dependent mate choice in a sex-specific manner. Wild-type female medaka consistently preferred familiar males.

However, oxytocin-deficient females rapidly accepted even unfamiliar males, demonstrating a complete loss of their natural familiarity-dependent preference. In contrast, oxytocin-deficient males initially displayed reduced courtship toward unfamiliar females, but their courtship frequency significantly increased with cohabitation, suggesting an altered response to familiarity. Furthermore, in triadic social interactions, oxytocin-deficient males exhibited enhanced mate-guarding behavior toward familiar females, indicating an exaggerated preference for established partners. Whole-brain transcriptome analyses revealed a consistent reduction in the expression of complement component C1q genes in both sexes, pointing to potential abnormalities in neurodevelopmental processes. Additionally, genes related to GABA metabolism were selectively altered in females, suggesting distinct sex-specific molecular pathways downstream of oxytocin signaling.