Postlactational Involution: Molecular Mechanisms and Relevance for Breast Cancer Development

Abstract

Mammary gland tissue changes appearance and functionality in diferent sequential steps. The tissue of virgin, pregnant, or lactating mammary glands changes controlled by inely regulated physiological processes. A fourth stage (involution), triggered upon weaning, involves remodeling, and the gland regresses to resemble a prepregnant stage. This highly complex process characterized by a high degree of epithelial cell death and tissue remodeling can be divided into phases, which can be independent of each other. The present article describes a variety of signaling pathway components, transcription factors, and mRNA stabilization proteins that play a role in the regulation of cell fate during the involution process. These molecular actors are inely related in health to trigger the delicate mechanism that govern involution after weaning, leaving the gland in a latent stage until needed again. Importantly, it has been shown that this process may contribute to cancer development in the years following childbirth, mainly because of the involvement of inlammatory and remodeling factors.

Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis

“…During post-partum mammary gland involution, the immune composition of the gland expands with an influx of infiltrating mast cells, macrophages, neutrophils, dendritic cells and natural killer cells, which remove apoptotic epithelial cells and support the remodeling of the gland (Guo et al, 2017;Kordon and Coso, 2017;O'Brien et al, 2010;Schwertfeger et al, 2001). Since our scRNAseq analyses suggested that fully involuted, post-pregnancy mammary glands are enriched for populations of NKT cells, we next utilized a series of flow cytometry analyses to validate this observation.…”

Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis

“…The post-partum mammary gland involution is marked by an influx of infiltrating mast cells, macrophages, neutrophils, dendritic cells, and natural killer cells, which remove apoptotic epithelial cells and support the remodeling of the gland (Guo et al, 2017;Kordon and Coso, 2017;O'Brien et al, 2010;Schwertfeger et al, 2001). Since our scRNA-seq analyses suggested that post-pregnancy mammary glands are enriched for populations of NKT cells, we next used a series of flow cytometry analyses to validate this observation.…”