Single Tissue Epigenetic Characterization in Sheep Foetuses

Environmental and nutritional signals during early life might affect fetal development with possible effects on important productive traits in livestock. Environmental and nutritional stressors are translated into epigenetic changes. DNA methylation and histone modification in regulatory and growth-related genes contribute to fetal programming for adult life. As a first and preliminary single organ epigenetic screen, we have carefully dissected embryonic ectodermic tissues (neurons, forebrain), mesenchymal cells (primarily fibroblasts, somites), and foregut endoderm cells (liver), from day 28 sheep foetuses collected after natural mating (day of mating: d0). The isolated tissues were snap frozen in liquid nitrogen and analysed for distribution of methylation of CpGs using whole-genome bisulfite sequencing (WGBS). Liver cells presented a lower methylation level than primordial neurons and fibroblasts. Patterns of methylation among the three tissues showed high conservation of hypo-methylated CpG islands, and a consistent level of methylation in regulative genetic elements. The three tissues differed in 398 differentially methylated regions (DMRs) overlapping CpG islands. DMRs interested several genes that showed a significant pathway enrichment for synaptic transmission, sensory perception of pain, behavioural response to nicotine, cardiac muscle tissue and heart growth, body morphogenesis, regulation of bone mineralization, cell senescence and cell aging. Numerous findings indicate that environmental and nutritional stressors affect productive traits, and even wellbeing in farm animals, through epigenetic changes in growth and developmental genes. Our work provides a “reference” epigenetic status of genes potentially involved in the maintenance and regulation of developmental differentiation that might be negatively affected by environmental and nutritional stressors.