Abstract
In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.
Highlights
The specific objectives of the current study are to (1) identify marker genes of brain cells and signaling pathways associated with the onset of rapid brain development in pig fetuses, (2) determine the influence of fetal sex on gene expression of the developing brain and (3) identify genes coordinately expressed between the pig placenta and fetal brain
57% of the variation in gene expression was explained by the first principal component
We identified 45 of these genes expressed either in the placenta or fetal brain that were related to ion transporters, further suggesting that ion transporter genes were tightly regulated in the placenta relative to the fetus during brain development
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The development of the fetal brain is regulated by complex and highly coordinated spatiotemporal processes [1,2,3]. The fetal brain develops in an accelerated manner after gestation day (GD) 60 [4]. Distinct regions of the brain are formed during rapid growth of the fetal brain [5]. The use of pigs as a large animal model for biomedical research is increasing [6,7,8]. Pig models have shown promising utilities in research relating to brain structure and function, including a better understating of neurodegenerative diseases in humans [9,10,11,12]
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