Schematic representation of the structure and morphological changes in mammary gland during lactation and involution.
(A) The lactation diagram shows a duct and tertiary branch with a single lobuloalveolar structure. The luminal ductal cells are derived primarily from long-lived progenitors that may be either hormone receptor positive (ER+/PR+) or hormone receptor negative (ER−/PR−), and the basal ductal cells are derived from lineage restricted unipotent progenitors. Alveolar luminal cells derive primarily from ER−/PR− progenitors while basal cells may derive from the ductal layer or be generated de novo from alveolar-specific progenitors. Myoepithelial cells are thinly stretched around the clusters of luminal cells and have a stellate structure. There may be a niche at the tips of tertiary branches that protects progenitors from cell death during involution (see text). The presence of binucleate cells, that have undergone a second round of DNA replication but have not divided, is indicated. Large milk fat globules (MFGs) are secreted, enveloped by the plasma membrane, while the milk protein caseins are secreted as micelles. (B) This diagram depicts a single alveolus at 24 h following forced involution. Activation of Stat3 initiates a fate switch in the secretory alveolar cells that now take back up secreted MFGs (indicated by red arrow) and shed cells (indicated by black arrow). This first phase of involution is reversible but after around 48 h, involution cannot be halted and the gland regresses almost completely to a pre-pregnant state. (C) By 6 days of involution, the alveoli have dramatically collapsed due to the extensive death of the luminal cells and remaining alveoli shrink back towards the ducts.