Rabaglino Maria B, Keller-Wood Maureen, Wood Charles E
Departamento de Reproducción Animal, Fac, Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
BMC Genomics. 2014 Nov 19;15(1):1001. doi: 10.1186/1471-2164-15-1001.
Major changes in gene expression occur in the fetal brain to modulate the function of this organ postnatally. Thus, factors can alter the genomics of the fetal brain, predisposing to neurological disorders later in life. We hypothesized that the physiological dynamics of the immune system transcriptome of the fetal brain during the last stage of gestation will reveal patterns of immune function and development in the developing brain. In this study we applied weighted gene co-expression analysis of microarrays performed on ovine fetal brain samples, to model the changes in gene expression throughout the second half of gestation.
Clusters of co-expressed genes that strongly increase in expression toward the first day of extra-uterine life are related to the hematopoietic lineage, while activation of immune pathways is induced after birth. Moreover, the pattern of gene expression suggests induction of tolerance mechanisms, probably necessary to protect highly produced proteins--such as myelin basic protein--from an autoimmune attack.
This study provides insight into the dramatic changes in gene expression that take place in the brain during the fetal life, especially during the last stage of gestation, and suggests that the immune system may have an important role in maturation of the fetal brain, which if disrupted or altered, could have negative consequences in postnatal life.
胎儿大脑中基因表达会发生重大变化，以调节该器官出生后的功能。因此，一些因素可能会改变胎儿大脑的基因组，使人在日后易患神经疾病。我们推测，妊娠最后阶段胎儿大脑免疫系统转录组的生理动态变化将揭示发育中大脑的免疫功能和发育模式。在本研究中，我们对绵羊胎儿脑样本进行微阵列加权基因共表达分析，以模拟妊娠后半期基因表达的变化。
在出生后第一天表达强烈增加的共表达基因簇与造血谱系相关，而免疫途径的激活在出生后被诱导。此外，基因表达模式表明诱导了耐受机制，这可能是保护高表达蛋白（如髓鞘碱性蛋白）免受自身免疫攻击所必需的。
本研究深入了解了胎儿期大脑中发生的基因表达的巨大变化，尤其是在妊娠最后阶段，并表明免疫系统可能在胎儿大脑成熟中发挥重要作用，如果这种作用受到干扰或改变，可能会对出生后的生活产生负面影响。
