Hippo-vgll3 signaling may contribute to sex differences in Atlantic salmon maturation age via contrasting adipose dynamics

Sexual maturation in Atlantic salmon entails a transition in energy utilization, governed in part by genes and environmental stimuli in sex-specific manner. Salmon males require less energy, in the form of adiposity, to mature compared to females and typically mature younger. Maturation age is also influenced in a sex-dependent fashion by the vgll3 genotype (vestigial-like 3), a co-factor in the Hippo pathway. The underlying molecular processes of sex-dependent maturation age, and how they interplay with adiposity and vgll3 genotypes, have remained unknown. To elucidate the molecular mechanisms underlying sex- and genotype-specific maturation differences, we investigated the association of early (E) and late (L) maturation vgll3 alleles and the transcriptional expression of > 330 genes involved in the regulation of the Hippo pathway and sexual maturation, and related to molecular signals in brain, adipose tissue, and gonads. The strongest effect of vgll3 genotype was observed in adipose tissue for females and in brain for males, highlighting a sex-specific expression difference in the main association of vgll3 genotype. Genes related to ovarian development showed increased expression in vgll3*EE compared to vgll3*LL females. Additionally, vgll3*EE females compared to vgll3*EE males exhibited reduced markers of pre-adipocyte differentiation and lipolysis yet enhanced expression of genes related to adipocyte maturation and lipid storage. Brain gene expression further showed sex-specific expression signals for genes related to hormones and lipids, as well as tight junction assembly. Overall, these sex-specific patterns point towards a greater lipid storage and slower energy utilization in females compared to males. These results suggest that Hippo-dependent mechanisms may be important mediators of sex differences in maturation age in salmon.