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

Background: Sexual maturation in Atlantic salmon entails a transition in energy utilization, regulated by genes and environmental stimuli in sex-specific manner. Males require less energy, in the form of adiposity, to mature and typically mature younger than females. 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 their interplay with adiposity and vgll3 genotypes, remain unclear. Methods: To elucidate the mechanisms underlying sex- and genotype-specific maturation differences, we investigated the association of early (E) and late (L) maturation vgll3 alleles with the transcription of > 330 genes involved in the regulation of the Hippo pathway and sexual maturation, and related molecular signals in brain, adipose, and gonads. Results: The strongest effect of vgll3 genotype was observed in adipose for females and in brain for males, highlighting sex-specific expression differences in association with vgll3 genotype. Genes related to ovarian development showed increased expression in vgll3*EE compared to vgll3*LL females. Moreover, 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. Conclusions: Overall, these sex-specific patterns point towards a greater lipid storage and slower energy utilization in females compared to males. These results suggest Hippo-dependent mechanisms may be important mediators of sex differences in maturation age in salmon.