Effects of enforced milk stasis on mammary gland epithelium, with special reference to changes in lysosomes and lysosomal enzymes

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Abstract Milk stasis was induced in the lactating mammary gland of the rat through ligation of the milk ducts on one side of the experimental animals while the nursing young were allowed to proceed with suckling on the other. Samples of tissues were prepared for biochemical assays of lysosomal enzymes, and for light and electron microscopy at different intervals during the experiment. A rapid milk stasis occurred after the milk ducts were ligated. Specific acitivities of four lysosomal enzymes (cathepsin D, acid phosphatase, aryl sulphatase, and β-glucuronidase) increased, as well as the total activities of the enzymes when calculated “per gland basis”. Total activities gained the maximum values between days 3 and 7. Activities of the four enzymes were low in the milk. Milk stasis led to enormous enlargement of the secretory alveoli with concurrent flattening of the mammary gland epithelium, formation of large intracellular vacuoles and autophagic vacuoles in the epithelial cells, necrosis of occasional epithelial cells, appearance of leucocytes and macrophages in the alveoli and epithelium, and, finally, slow general involution of the mammary gland. Acid phosphatase activity was demonstrated histochemically in the lysosomes and autophagic vacuoles of the epithelial cells and in the lysosomes of macrophages. In addition, reaction product was found in the large intracellular vacuoles which often contained protein droplets, suggesting that the stagnant milk was degraded, at least in part, in newly formed lysosome-equivalents in the epithelium. The results were interpreted to indicate that isolated milk stasis ( a ) is able to produce degenerative alterations in the mammary gland epithelium and epithelial cells; ( b ) brings about an increase in the concentration and total activities of lysosomal enzymes in the mammary gland; ( c ) is noxious enough to give rise to tardy gross involution of the gland.