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Histological analysis of mammary gland remodeling caused by lipopolysaccharide in lactating mice

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Abstract

The mammary alveolus is a highly specialized structure that secretes milk for suckling infants during lactation. The secreting alveolus consists in alveolar epithelial cells (AECs) and myoepithelial cells and is surrounded by microvascular endothelial cells, adipocytes and several immune cell types such as macrophages and neutrophils. During normal lactation, these cells play distinct roles needed to maintain the secretory ability of the mammary alveolus. However, inflammation resulting from pathogenic bacterial infections causes structural and functional regression of the secreting alveolus in the lactating mammary gland. We initiated artificial inflammation in the mammary glands of lactating mice by injecting lipopolysaccharide (LPS), as a mammary inflammation model and investigated, by immunohistochemical analysis, the early response of the cells constituting and surrounding the alveolus. Some AECs sloughed away from the alveolar epithelial layer and showed progression of apoptosis detected by immunostaining of cleaved caspase-3 after LPS injection. Adipocytes exhibited transient shrinkage and re-accumulation of lipid droplets, although the numbers of adipocytes did not demonstrate a significant difference. Activation of F4/80-positive cells around the mammary alveolus was observed 3 h after LPS injection. However, the recruitment of CD11b-positive cells into the alveolar lumen was not observed until 12 h after LPS injection. Myoepithelial cells were contracted after LPS injection. LPS injection around the alveolus did not induce any detectable structural changes in capillaries surrounding the alveolus. Thus, cell-specific behavior and tissue remodeling of the alveolus occur after LPS injection in a time-dependent manner.

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Acknowledgements

We thank Atsushi Numata, Laboratory of Dairy Food Science, Research Faculty of Agriculture, Hokkaido University for helpful discussions.

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Correspondence to Ken Kobayashi.

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This work was supported by a Grant-in-Aid for Young Scientists (24780281) from the Japan Society of Promotion of Science and a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science, and Technology.

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Kobayashi, K., Uejyo, T., Oyama, S. et al. Histological analysis of mammary gland remodeling caused by lipopolysaccharide in lactating mice. Cell Tissue Res 354, 495–506 (2013). https://doi.org/10.1007/s00441-013-1688-5

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