Autophagy in the uterine vessel microenvironment: Balancing vasoactive factors

Abstract

Autophagy, which has the literal meaning of self-eating, is a cellular catabolic process executed by arrays of conserved proteins in eukaryotes. Autophagy is dynamically ongoing at a basal level, presumably in all cells, and often carries out distinct functions depending on the cell type. Therefore, although a set of common genes and proteins is involved in this process, the outcome of autophagic activation or deficit requires scrutiny regarding how it affects cells in a specific pathophysiological context. The uterus is a complex organ that carries out multiple tasks under the influence of cyclic changes of ovarian steroid hormones. Several major populations of cells are present in the uterus, and the interactions among them drive complex physiological tasks. Mouse models with autophagic deficits in the uterus are very limited, but provide an initial glimpse at how autophagy plays a distinct role in different uterine tissues. Herein, we review recent research findings on the role of autophagy in the uterine mesenchyme in mouse models.

Repopulation of autophagy-deficient stromal cells with autophagy-intact cells after repeated breeding in uterine mesenchyme-specific Atg7 knockout mice

“…Autophagic defects are generally visualized by examining SQSTM1 accumulation [ 1 ] because it is highly upregulated when autophagic flux is blocked [ 12 ]. In Atg7 f/f (wild-type) virgin uteri, autophagy is generally active, and there was no visible accumulation of SQSTM1 ( Figure 1 , virgin Atg7 f/f ), which was consistent with the results of our previous study [ 2 ].…”

“…While it takes place at a basal level in all tissues, the consequences of autophagy deficiency vary significantly depending on the tissue type. In the mouse uterus, autophagy levels differ between epithelial and mesenchymal tissues [ 1 ]. We have previously demonstrated that the uterine mesenchyme, including the stroma, myometrium, and endothelial smooth muscle cells, is a site of active autophagic turnover in mice [ 2 ].…”