母体采食量限制阻抑羔羊次级肌纤维发育的代谢记忆机制

Mutton production in southern Xinjiang is often faced with the shortage of feed in winter and spring, which leads to intake insufficient of pregnant ewes, resulting in the miniaturization of offspring lambs, growth retardation, and meat production decline. It has been found that feed intake restriction of pregnant ewes damage the development of fetal secondary muscle fibers in long term, this metabolic memory of the offspring leads to muscle fiber dysplasia of lamb at birth and in the adult, can be used to explain the phenomenon of miniaturization of lambs, but its biological mechanism remains to be unclear. This project focuses on this scientific issue of feed intake restriction in ewes damaging the development of secondary muscle fibers in offspring, through mimicking the status of maternal feed intake restriction under experimental condition, to construct animal models of short- or long-term effects in the fetal or growing periods respectively. From the aspects of protein and energy metabolism, it mainly concentrates on the variation in tissue morphology, metabolites, protein expression, mRNA expression, and epigenetic modification of DNA and histone related to secondary muscle fiber development. This project will be helpful to understand how the maternal nutrient environment during pregnancy mediates the development of fetal muscle, and how this metabolic memory of the muscle development lasts at the later stage of life. It can provide a scientific basis for appropriate nutrition manipulation strategy to improve the meat performance of miniaturized lambs.

南疆肉羊业常面临冬春季饲草缺乏问题，导致妊娠母羊摄食不足，产生羔羊体型小型化、生长发育迟滞和产肉性能降低现象。研究发现妊娠母羊采食量受限对胎儿肌肉次级肌纤维发育造成长久记忆性的损害，这种代谢记忆导致后代在出生及成年后肌纤维发育不良，造成羔羊体型小型化现象；但其生物学机制尚待阐明。项目围绕母羊采食量受限损害后代次级肌纤维发育这一科学问题，通过实验模拟妊娠中期母羊采食量受限状况，在子代胎儿期和生长期构建短期和长期效应动物模型。主要从蛋白质和能量代谢角度，解析与次级肌纤维发育受阻密切相关的组织形态变化、生理生化指标响应、蛋白质和mRNA表达变化以及组蛋白和DNA甲基化修饰差异，旨在揭示母体采食量限制阻抑后代肌肉发育的短期和长期代谢记忆机理。为深入理解妊娠期母体营养环境如何介导胎儿肌肉程序化发育并在生命后期肌肉如何持续拥有代谢记忆现象，以及采用恰当营养调控策略改善小型化羔羊产肉性能提供科学依据。

母体营养不足导致的肌肉发育受阻现象仍是我国现代肉羊养殖中面临的问题。项目基于妊娠母羊营养缺乏导致子代羔羊体型小型化、生长发育迟滞和产肉性能降低现象，围绕母羊采食量受限损害后代次级肌纤维发育这一科学问题，通过模拟妊娠中期母羊采食量40%受限状况，在子代胚胎阶段和断奶阶段构建动物模型，从蛋白质和能量代谢角度，解析与次级肌纤维发育受阻密切相关的组织形态变化、血液生理生化指标响应、蛋白质和mRNA表达变化以及肌生成因子DNA甲基化修饰差异。研究发现妊娠中期40%母体限饲影响胎儿和羔羊心脏和肝脏器官发育，子代出生后呈现节俭型表型。母体限饲编程子代肌肉组织能量代谢及肌蛋白合成，其机制可能与PKA-CREB-CLOCK路径关联。受限子代的后肢肌纤维类型更多地向I和IIA型转变，呈现出肌纤维发育编程现象。项目在能量和蛋白质代谢层面揭示了母体营养受限条件下影响胎儿和断奶期羔羊骨骼肌发育的部分机制，这些结果为进一步解析在其他生命发育时期母体营养不足影响后代肌肉生长的生理代谢机制奠定了基础，也为肌肉发育程序化编程的共性机制研究指明方向。

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