Paten Amy M, Duncan Elizabeth J, Pain Sarah J, Peterson Sam W, Kenyon Paul R, Blair Hugh T, Dearden Peter K
Laboratory for Evolution and Development, Genetics Otago, Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin, Aotearoa, New Zealand.
International Sheep Research Centre, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, Aotearoa, New Zealand.
BMC Genomics. 2015 Oct 5;16:748. doi: 10.1186/s12864-015-1947-9.
The mammary gland is a dynamic organ that undergoes dramatic physiological adaptations during the transition from late pregnancy to lactation. Investigation of the molecular basis of mammary development and function will provide fundamental insights into tissue remodelling as well as a better understanding of milk production and mammary disease. This is important to livestock production systems and human health. Here we use RNA-seq to identify differences in gene expression in the ovine mammary gland between late pregnancy and lactation.
Between late pregnancy (135 days of gestation ± 2.4 SD) and lactation (15 days post partum ± 1.27 SD) 13 % of genes in the sheep genome were differentially expressed in the ovine mammary gland. In late pregnancy, cell proliferation, beta-oxidation of fatty acids and translation were identified as key biological processes. During lactation, high levels of milk fat synthesis were mirrored by enrichment of genes associated with fatty acid biosynthesis, transport and lipogenesis. Protein processing in the endoplasmic reticulum was enriched during lactation, likely in support of active milk protein synthesis. Hormone and growth factor signalling and activation of signal transduction pathways, including the JAK-STAT and PPAR pathways, were also differently regulated, indicating key roles for these pathways in functional development of the ovine mammary gland. Changes in the expression of epigenetic regulators, particularly chromatin remodellers, indicate a possible role in coordinating the large-scale transcriptional changes that appear to be required to switch mammary processes from growth and development during late pregnancy to synthesis and secretion of milk during lactation.
Coordinated transcriptional regulation of large numbers of genes is required to switch between mammary tissue establishment during late pregnancy, and activation and maintenance of milk production during lactation. Our findings indicate the remarkable plasticity of the mammary gland, and the coordinated regulation of multiple genes and pathways to begin milk production. Genes and pathways identified by the present study may be important for managing milk production and mammary development, and may inform studies of diseases affecting the mammary gland.
乳腺是一个动态器官，在从妊娠晚期到泌乳期的转变过程中会经历显著的生理适应性变化。对乳腺发育和功能的分子基础进行研究，将为组织重塑提供基本见解，并有助于更好地理解乳汁生成和乳腺疾病。这对畜牧生产系统和人类健康都很重要。在此，我们使用RNA测序来鉴定妊娠晚期和泌乳期绵羊乳腺中基因表达的差异。
在妊娠晚期（妊娠135天±2.4标准差）和泌乳期（产后15天±1.27标准差）之间，绵羊基因组中13%的基因在绵羊乳腺中差异表达。在妊娠晚期，细胞增殖、脂肪酸的β氧化和翻译被确定为关键生物学过程。在泌乳期，与脂肪酸生物合成、转运和脂肪生成相关的基因富集反映出高水平的乳脂肪合成。内质网中的蛋白质加工在泌乳期富集，可能是为了支持活跃的乳蛋白合成。激素和生长因子信号传导以及信号转导途径的激活，包括JAK-STAT和PPAR途径，也受到不同的调节，表明这些途径在绵羊乳腺功能发育中起关键作用。表观遗传调节因子，特别是染色质重塑因子表达的变化，表明其在协调大规模转录变化中可能发挥作用，这些变化似乎是将乳腺过程从妊娠晚期的生长发育转换为泌乳期的乳汁合成和分泌所必需的。
在妊娠晚期乳腺组织形成与泌乳期乳汁生成的激活和维持之间切换，需要对大量基因进行协调转录调控。我们的研究结果表明乳腺具有显著的可塑性，以及多个基因和途径为启动乳汁生成的协调调控。本研究鉴定出的基因和途径可能对管理乳汁生成和乳腺发育很重要，并可能为影响乳腺的疾病研究提供信息。
