山羊妊娠期营养限制对胎儿骨骼发育的程序性抑制及其机理研究

In China, the production of ruminants is greatly influenced by seasonal conditions as the deficient supply of forage and low nutritive value of pasture would result in maternal nutritional deficiency in dry season. It has been reported that maternal nutritional deficiency would program the development of fetus, which is associated with nutritional restricted time. Moreover, as the supporting tissue for muscle, bone development plays a vital role on the growth and production performance of domestic animals. Therefore, this project will be conducted with goats to investigate the effects of maternal feed intake restriction during early, middle and late gestation, respectively, on fetal bone development and metabolism by assessing bone morphology and metabolic parameters of bone development. The mRNA expression levels of bone metabolism genes and the key protein expression levels in some pathways related to bone development will also be determined to explore the programming mechanism induced by maternal undernutrition at molecular level. The sensibility of nutritional restricted periods to fetal bone development will be stated upon the variable results of fetal bone programming induced by maternal feed intake restriction at different time at morphological, physiological and molecular levels. It will be helpful to reduce the programming of fetal skeleton induced by maternal nutrients deficiency in goats and other ruminants, and to provide guidance strategies for nutrition manipulation at different gestation stages.

我国反刍家畜养殖受季节性影响严重，冬春季节由于草料供应不足，使得妊娠家畜面临营养不足的风险。而妊娠期的营养不足会程序性地抑制胎儿发育，且这种抑制作用与营养不足发生的时期密切相关。骨骼作为肌肉的支撑组织，对家畜正常发育及其生产性能至关重要。本项目拟以山羊为实验动物，研究妊娠前、中、后三个不同时期采食限制对胎羊骨骼的形态发育和骨骼发育相关的代谢指标，以及骨骼代谢相关基因表达水平和骨骼分化相关信号通路中关键蛋白稳定性的影响，以期初步探讨骨骼程序化抑制的分子机理。从形态、生理和分子水平层次阐明妊娠期营养不足对胎羊骨骼发育的抑制作用，并综合分析妊娠期三个不同时期采食限制对胎羊骨骼发育影响程度的差异，阐释胎羊骨骼发育响应母体营养不足的敏感性时期，为降低孕期营养不足对山羊或其它种类反刍动物胎儿骨骼发育的程序化抑制，制定各阶段相应的合理营养调控措施提供科学依据。

我国反刍家畜养殖受季节性影响严重，冬春季节由于草料供应不足，使得妊娠家畜面临营养不足的风险。而妊娠期的营养不足会程序性地抑制胎儿发育，且这种抑制作用与营养不足发生的时期密切相关。骨骼作为肌肉发育支撑组织，对家畜正常发育及其生产性能至关重要。通过分别开展妊娠前期、妊娠中期和妊娠后期山羊营养限饲（40%采食量限制）试验，比较营养限饲组与正常营养组山羊后代胎羊骨骼形态发育、骨骼生理代谢和骨骼代谢相关基因等指标的差异，同时对母羊代谢状态和胎儿生长环境（羊水和尿囊液）氨基酸水平进行了测定。结果发现：1）不同妊娠阶段40%采食量限制对母羊的生长发育均无显著影响，表明营养限制程度不高；2）对于胎儿生长发育，妊娠前期营养限制使得母羊成骨代谢活动有增强趋势，胎羊破骨代谢减弱，促进胎儿及其骨骼的生长；妊娠中期营养限制对骨骼发育和骨代谢无显著影响；妊娠后期营养限制抑制胎儿的生长，但不影响骨骼生长，结果表明在不良营养环境下，骨骼发育是胎儿优先保障的器官；3）胎羊骨骼发育与母羊代谢状态密切相关，在母羊营养限制状态下，通过引起母羊代谢活动以及宫内发育环境（如羊水和尿囊液）氨基酸水平的改变，可能是胎羊骨骼发育发生相应改变的主要原因；4）综合分析妊娠期三个不同时期采食限制对胎羊发育影响程度的差异，结果表明妊娠后期为胎羊发育响应母体营养不足的最敏感性时期，在反刍家畜妊娠后期进行适当补饲将有效降低孕期营养不足对反刍动物胎儿发育的不利影响。