Evolutionary divergence and expression dynamics of the progestin receptor system: Sex-specific responses to exogenous...

Progestin signaling in teleosts is mediated by a diverse receptor repertoire that has been further expanded after genome duplication. However, how these receptors are organized and respond to exogenous stimulation within a single species remains poorly understood. Here, we characterized the progestin receptor system (PRS) in Spinibarbus hollandi through genome-wide identification, evolutionary analysis, basal expression profiling, molecular docking, and levonorgestrel (LNG) treatment experiments. We identified 14 PRS genes, including lineage-specific loss of paqr5b and retention of duplicated paqr6, indicating uneven post-duplication trajectories within this receptor family. Basal expression profiling further revealed tissue-specific patterns of PRS components across the gonad, liver, and brain. Under LNG treatment, somatic growth remained largely stable, whereas gonadal development showed clear sex-biased responses. Females exhibited ovarian regression and reduced gonadosomatic index across all treatment groups, whereas males retained active spermatogenesis at low and medium concentrations and developed degenerative lesions mainly at the highest concentration. These phenotypic differences were accompanied by tissue-specific shifts in the overall PRS expression landscape and by non-uniform transcriptional responses among selected PRS members, including shared downregulation of paqr7a, a female-specific decline but relative male stability of paqr7b, inducible hepatic expression of pgr1, and brain upregulation of pgrmc1. Together, these findings indicate that the PRS of S. hollandi has diverged at both the repertoire and expression levels and responds to exogenous progestin treatment in a tissue- and sex-dependent manner.