Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes

Author:

Kremsky Isaac,Ma Qingyi,Li Bo,Dasgupta Chiranjib,Chen Xin,Ali Samir,Angeloni Shawnee,Wang Charles,Zhang Lubo

Abstract

Abstract Background Fetal hypoxia causes vital, systemic, developmental malformations in the fetus, particularly in the brain, and increases the risk of diseases in later life. We previously demonstrated that fetal hypoxia exposure increases the susceptibility of the neonatal brain to hypoxic-ischemic insult. Herein, we investigate the effect of fetal hypoxia on programming of cell-specific transcriptomes in the brain of neonatal rats. Results We obtained RNA sequencing (RNA-seq) data from neurons, microglia, oligodendrocytes, A2B5+ oligodendrocyte precursor cells, and astrocytes from male and female neonatal rats subjected either to fetal hypoxia or control conditions. Substantial transcriptomic responses to fetal hypoxia occurred in neurons, microglia, oligodendrocytes, and A2B5+ cells. Not only were the transcriptomic responses unique to each cell type, but they also occurred with a great deal of sexual dimorphism. We validated differential expression of several genes related to inflammation and cell death by Real-time Quantitative Polymerase Chain Reaction (qRT-PCR). Pathway and transcription factor motif analyses suggested that the NF-kappa B (NFκB) signaling pathway was enriched in the neonatal male brain due to fetal hypoxia, and we verified this result by transcription factor assay of NFκB-p65 in whole brain. Conclusions Our study reveals a significant impact of fetal hypoxia on the transcriptomes of neonatal brains in a cell-specific and sex-dependent manner, and provides mechanistic insights that may help explain the development of hypoxic-ischemic sensitive phenotypes in the neonatal brain.

Funder

Foundation for the National Institutes of Health

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology

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