Background
The socially-controlled sex change that certain fishes are capable of, is an extreme form of reproductive plasticity in which a social cue induces coordinated changes in behaviour, brain and, ultimately, gonadal state. Although gonadal remodelling has been well characterised, the neural mechanisms that initiate sex change remain poorly understood. We used the protogynous (changing sex from female to male) New Zealand spotty wrasse (Notolabrus celidotus) to investigate how hypothalamic gene expression changes across female, sex-changing and male states.

Methods
Wild-caught spotty wrasse were housed in social groups comprising one male and four females. Brains were collected from females, males and individuals undergoing female-to-male sex change (n = 3 per state), with gonadal histology used to confirm reproductive status. Ten-micrometre coronal sections through the hypothalamus were analysed using the Visium HD 3′ spatial transcriptomics platform. Data were examined using spatial clustering, cell-type annotation, differential-expression and pathway-enrichment analyses.

Results
Spatial transcriptomic profiling revealed pronounced region-specific differences among reproductive states. Females, males and sex-changing fish displayed distinct molecular signatures, while sex-changing brains showed transitional expression patterns that were not simply intermediate between female and male states. The brain aromatase transcript, cyp19a1b, was concentrated in radial glial-like cell populations and showed lower expression across sex change, whereas several markers associated with radial glial plasticity showed the opposite pattern. Genes involved in neuropeptide signalling, synaptic plasticity and stress responses also varied spatially among reproductive states.

Conclusion
These data provide the first spatially resolved molecular map of the sex-changing fish hypothalamus and identify candidate neural cell populations and pathways associated with reproductive transformation. The findings advance our understanding of how the brain mediates socially-controlled sex change and identifies cell types that can be targeted to induce or prevent sex change in fish.