Prenatal hypoxia exposure induced methylomic and transcriptomic alterations in rat hearts [BiSulfite-seq]

Antenatal hypoxia has critial impacts on fetal heart development. The molecular mechanism of the antenaltal hypoxia effect on the heart development is still unknown. We performed DNA methylome and transcriptome analyses of antenatal hypoxia induced rat fetal and adult offspring hearts to understand the hypoxia-mediated epigenomic programming in the heart development. Heart tissue from fetal (E21) and adult rat (5 months old) were collected. mRNA and genomic DNA methylation profiles of the heart tissue were generated by RNAseq and reduced representation bisulfite seuqencing (RRBS) techniques. We found 323 and 112 differential expressed genes between control and hypoxia groups in the fetal and adult hearts, respectively. Meanwhile, 2828 and 2193 differential methylated regions were identified in the fetal and adult hearts. Furthermore, opposite gobal DNA methylation pattern changes in transcription start site regions (TSS ± 1kb) were observed between fetal and adult hearts. Combining transcriptome, data indicates a significant difference in the responding genes and pathways between fetal and adult hearts in responding to the antenatal hypoxia. Our study provides an initial framework and new insights into fetal hypoxia-mediated epigenetic programming of pro-inflammatory phenotype in the heart development, linking antenatal stress, and developmental programming of heart vulnerability to disease later in life. Fetal (E21) heart tissues from control (n=3) and hypoxia (n=3) Sprague-Dawley (SD) rats were collected for methylome and transcriptome analysis. Adult male (5 months old) heart tissues from control (n=6) and hypoxia (n=6) SD rats were obtained for methylome analysis. Adult male and female (5 months old) heart tissues from control (n=5 per gender) and hypoxia (n=5 per gender ) SD rats were used for transcriptome analysis.