Pregnancy |
The morphogenesis of mammary ducts during early pregnancy and differentiation of the mammary alveolus during late pregnancy |
Genes associated with cell cycle, cell proliferation, and the immune response |
[55,56,57] |
Initiation of lactation |
Mammary differentiation, and proliferation, progressive expression of milk protein, and the secretion of precolostrum. The closure of the tight junctions between alveolar cells and the formation and secretion of colostrum and milk |
Up-regulation of genes involved in milk synthesis concomitant with the inhibition of those related to cell proliferation. Some immune- and development-related miRNA highly expressed in colostrum and mammary glands |
[40,55,58,59] |
Middle lactation |
Maintaining the number and activity of milk secreting cells |
Milk constituents and milk synthesis-related pathways that are persistently expressed |
[5,7,51,52,60] |
Involution |
The cessation of secretory activity and the reabsorption of milk residue, followed by a relatively static period. Invasion of leukocytes, increased epithelial cell death (through apoptosis or autophagy), and/or proliferation of connective tissue |
A strong up-regulation of immune and antioxidant-related genes, and down-regulation of milk synthesis-related gene expression |
[46,61] |