Hoffman M L, Reed S A, Pillai S M, Jones A K, McFadden K K, Zinn S A, Govoni K E
J Anim Sci. 2017 May;95(5):2222-2232. doi: 10.2527/jas.2016.1229.
Poor maternal nutrition during gestation has been linked to poor growth and development, metabolic dysfunction, impaired health, and reduced productivity of offspring in many species. Poor maternal nutrition can be defined as an excess or restriction of overall nutrients or specific macro- or micronutrients in the diet of the mother during gestation. Interestingly, there are several reports that both restricted- and over-feeding during gestation negatively affect offspring postnatal growth with reduced muscle and bone deposition, increased adipose accumulation, and metabolic dysregulation through reduced leptin and insulin sensitivity. Our laboratory and others have used experimental models of restricted- and over-feeding during gestation to evaluate effects on early postnatal growth of offspring. Restricted- and over-feeding during gestation alters body size, circulating growth factors, and metabolic hormones in offspring postnatally. Both restricted- and over-feeding alter muscle growth, increase lipid content in the muscle, and cause changes in expression of myogenic factors. Although the negative effects of poor maternal nutrition on offspring growth have been well characterized in recent years, the mechanisms contributing to these changes are not well established. Our laboratory has focused on elucidating these mechanisms by evaluating changes in gene and protein expression, and stem cell function. Through RNA-Seq analysis, we observed changes in expression of genes involved in protein synthesis, metabolism, cell function, and signal transduction in muscle tissue. We recently reported that satellite cells, muscle stem cells, have altered expression of myogenic factors in offspring from restricted-fed mothers. Bone marrow derived mesenchymal stem cells, multipotent cells that contribute to development and maintenance of several tissues including bone, muscle, and adipose, have a 50% reduction in cell proliferation and altered metabolism in offspring from both restricted- and over-fed mothers. These findings indicate that poor maternal nutrition may alter offspring postnatal growth by programming stem cell populations. In conclusion, poor maternal nutrition during gestation negatively affects offspring postnatal growth, potentially through impaired stem and satellite cell function. Therefore, determining the mechanisms that contribute to fetal programming is critical to identifying effective management interventions for these offspring and improving efficiency of production.
孕期母体营养状况不佳与许多物种后代的生长发育不良、代谢功能障碍、健康受损及生产力下降有关。母体营养状况不佳可定义为孕期母亲饮食中总体营养素或特定常量营养素或微量营养素的过量或受限。有趣的是,有几份报告指出,孕期饮食受限和过量喂养都会对后代出生后的生长产生负面影响,表现为肌肉和骨骼沉积减少、脂肪堆积增加以及通过降低瘦素和胰岛素敏感性导致代谢失调。我们实验室及其他机构已利用孕期饮食受限和过量喂养的实验模型来评估对后代出生后早期生长的影响。孕期饮食受限和过量喂养会改变后代出生后的体型、循环生长因子和代谢激素。饮食受限和过量喂养都会改变肌肉生长、增加肌肉中的脂质含量,并导致生肌因子表达发生变化。尽管近年来母体营养状况不佳对后代生长的负面影响已得到充分描述,但导致这些变化的机制尚未完全明确。我们实验室一直致力于通过评估基因和蛋白质表达以及干细胞功能的变化来阐明这些机制。通过RNA测序分析,我们观察到肌肉组织中参与蛋白质合成、代谢、细胞功能和信号转导的基因表达发生了变化。我们最近报告称,卫星细胞即肌肉干细胞,在饮食受限母亲的后代中其生肌因子表达发生了改变。骨髓来源的间充质干细胞是一种多能细胞,对包括骨骼、肌肉和脂肪在内的多种组织的发育和维持有贡献,在饮食受限和过量喂养母亲的后代中,其细胞增殖减少50%,代谢也发生改变。这些发现表明,母体营养状况不佳可能通过对干细胞群体进行编程来改变后代出生后的生长。总之,孕期母体营养状况不佳会对后代出生后的生长产生负面影响,可能是通过损害干细胞和卫星细胞功能。因此,确定导致胎儿编程的机制对于确定针对这些后代的有效管理干预措施以及提高生产效率至关重要。