农业生物技术学报2025，Vol.33Issue(12)：2639-2653,15.DOI:10.3969/j.issn.1674-7968.2025.12.008
PGF2α对绵羊黄体期不同阶段黄体组织铁代谢、铁死亡和自噬的影响
Effects of PGF2α on Iron Metabolism,Ferroptosis and Autophagy in Luteal Tissue During Different Stages of the Luteal Phase in Sheep(Ovis aries)
摘要
Abstract
Prostaglandin F2α(PGF2α)plays a critical role in luteolysis by mediating apoptosis of luteal cells through its receptor.However,PGF2α does not exhibit pro-apoptotic effects on early-stage corpus luteum(CL)cells.Ferroptosis,a recently discovered form of programmed cell death driven by lipid peroxidation and dependent on iron ions,remains unclear in its role during PGF2α-mediated apoptosis of luteal cells at different developmental stages.This study investigated the impacts of PGF2α on iron content,ferroptosis,and autophagy-related gene expression in ovine CL during early,mid,and late luteal phases.Forty-eight synchronized healthy ewes(Ovis aries)were randomly allocated into 6 groups(experimental vs.control for each phase).Experimental groups received 0.15 mg PGF2α on day 5(early),9(mid),and 13(late luteal phase),while controls received saline at corresponding time points.CL tissues were collected 3 h post-injection for analyses.Results revealed that PGF2α significantly increased iron content throughout the luteal phase(P＜0.05).Phase-specific responses were observed:Early-phase PGF2α upregulated anti-ferroptosis genes(SLC7A11,NRF2,FTH1),pro-ferroptosis gene ACSL4,and ferroptosis-related proteins(Ferritin,GPX4,SLC7A11,LC3B,NCOA4),while downregulating GPX4 and HSPA8(P＜0.05).Mid-phase treatment enhanced SLC7A11,ACSL4,ATG5,TPD52,HSPA5,HSPA8,and corresponding proteins,but suppressed NRF2(P＜0.05).Late-phase administration upregulated P53,ACSL4,GPX4,ATG5,HSPA5,HSPA8 genes and GPX4/SLC7A11/LC3B proteins,while downregulating NRF2,FTH1,and Ferritin(P＜0.05).Mechanistic analysis revealed temporal regulation patterns:Early-phase PGF2α enhanced antioxidant defenses via SLC7A11/NRF2/FTH1 axis and iron sequestration to resist ferroptosis;mid-phase activated ACSL4-mediated pro-oxidative environment and ATG5-dependent autophagy,accelerating lipid peroxidation;late-phase triggered P53 activation,NRF2 suppression,and ACSL4 amplification,culminating in iron overload and irreversible ferroptosis-driven luteolysis.These findings demonstrate that PGF2α orchestrates sequential regulation of ferroptosis and autophagy pathways to drive CL transition from early antioxidant protection to terminal regression.This study provides theoretical basis for interventions in luteal dysfunction.关键词
绵羊/前列腺素F2α(PGF2α)/黄体期/铁死亡/自噬Key words
Sheep/Prostaglandin F2α(PGF2α)/Luteal phase/Ferroptosis/Autophagy分类
农业科技引用本文复制引用
甄至涵,刘月琴,张英杰,康佳,尹江艳,李傲,李宇,岳思聪,刘晓娜,段春辉,王媛..PGF2α对绵羊黄体期不同阶段黄体组织铁代谢、铁死亡和自噬的影响[J].农业生物技术学报,2025,33(12):2639-2653,15.基金项目
国家肉羊产业技术体系(CARS-38) （CARS-38）
