孕期母体不良营养状况对胎儿下丘脑神经前体细胞增殖和分化的影响及其作用机理研究

Recent years, research results have shown that metabolic diseases in adulthood could be related to maternal nutrition of early stage of fetal development. Our previous results have shown that chronic high-fat-diet feeding led to not only depletion but also neurogenic impairment of hypothalamic neural progenitor cells in adult mouse. Based on our findings, we postulate that the metabolic diseases are closely related to the early development of fetal hypothalamus. Poor maternal nutrition during pregnancy may lead to abnormal proliferation and differentiation of fetal hypothalamic neural progenitor cells and will evenly result into dysfunction of hypothalamus in offspring. In this proposal, we plan to establish poor maternal nutrition mouse models. In these mouse models, we will study the proliferation and differentiation of fetal hypothalamic neural progenitor cells both in vivo and in vitro, analyze gene expression and key signaling pathway’s activities involved in proliferation and differentiation and explore the underlying regulatory mechanisms. Our findings in this proposal will reveal the effect and mechanism of poor maternal nutrition on fetal hypothalamic neural progenitor cell’s proliferation and differentiation, and provide a theoretical basis for the pathogenesis of metabolic diseases.

近年来的研究表明，成年代谢性疾病与其胚胎发育期母体营养状况密切相关。我们在以前的研究中发现，在长期食用高脂肪食物的肥胖小鼠下丘脑中，神经前体细胞数目减少，且功能紊乱，下丘脑神经再生能力受损。根据这个现象，我们认为胎儿起源的成人代谢性疾病与胎儿下丘脑的早期发育密切相关，母体在怀孕期间的营养不良能造成胎儿下丘脑神经前体细胞增殖和分化功能紊乱，导致下丘脑发育异常。本课题拟以这个为线索，建立孕期营养不良小鼠模型，首先在体内和体外研究不同小鼠模型中胎儿下丘脑神经前体细胞增殖和分化的差异，然后进一步分析与增殖和分化相关的基因表达和信号通路的激活状态，最后探讨其内在的调控机制。我们的研究结果将揭示母体不良营养状况对胎儿下丘脑神经前体细胞增殖和分化的影响及调节机制，为代谢病的发病机理提供理论依据。