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

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. Overall design: Pregnant Sprague-Dawley (SD) rats (Charles River Laboratories, Portage, MI, USA) were randomly divided into two groups: (i) the normoxic control and (ii) hypoxic exposure (10.5% O2) from Day 15 to Day 21 of gestation, as we previously described [11, 34-37]. The pups were sacrificed at postnatal day 7, and the brains were collected for cell sorting. Five types of brain cells (microglia, neurons, astrocytes, oligodendrocytes, A2B5+ glia precursor cells) were sorted from P7 pups using magnetic-activated cell sorting (MACS) technology. Total RNA was isolated from each cell type using the Qiagen miRNeasy kit (Cat # 217004) following manufacturer's protocol.