湖羊性早熟与精子发生的HPT轴磷酸化调控机制OA

Hu sheep is a world-renowned multiparous breed characterized by exceptional germplasm traits,including precocious puberty,and high fecundity.However,the post-translational regulatory mechanisms orchestrating the highly efficient operation of their Hypothalamus-Pituitary-Testis(HPT)axis remain elusive.In this study,using Hu sheep and three introduced mutton sheep breeds(Southdown,Poll Dorset,and Suffolk)as research objects,we inte-grated histological analysis with 4D-DIA deep phosphoproteomics to systematically dissect the kinase signaling net-works driving male high fecundity.Histological observations revealed that the seminiferous tubule diameter in 6-month-old ram Hu sheep was significantly larger than that in the other mutton sheep breeds(P<0.001),exhibiting a more advanced maturation of the germinal epithelium.42 433 high-confidence phosphorylation sites were identified,and a comprehensive phosphoproteomic atlas of the ovine HPT axis was constructed.Meanwhile,this study uncovered that the Hu sheep HPT axis achieves systemic optimization of reproductive functions via tissue-specific phosphopro-teomic remodeling:the hypothalamus features high-intensity activation of MAPK cascades and phosphorylation of syn-aptic plasticity-related proteins,suggesting a mechanism to rapidly trigger precocious puberty by lowering the neuro-nal excitation threshold;the pituitary specifically activates a UBQLN2-centered ubiquitination quality control system and a cAMP-PKA-AMPK metabolic coupling network to adapt to the high-throughput load of hormone synthesis and secretion;the testis displays a distinct"nuclear-localized"regulatory signature,enhancing DNA repair capacity via con-formational activation of RAD23A,establishing strict cell cycle checkpoints through differential phosphorylation of CDK1/CDK2,and synergizing with Src family kinases to remodel blood-testis barrier homeostasis,thereby driving ef-ficient spermatogenesis while safeguarding genomic stability.This study elucidates the molecular regulatory mecha-nisms of the Hu sheep HPT axis from the dimension of phosphorylation,offering novel theoretical insights into high-fecundity traits in ruminants and providing potential precise targets for ovine molecular breeding.