Apoptosis as the Mode of Uterine Epithelial Cell Death during Embryo Implantation in Mice and Rats1

Abstract

An ultrastructural study of mouse and rat embryo implantation sites was undertaken to determine whether the uterine luminal epithelial cells surrounding the blastocyst exhibited the morphologic characteristics of apoptotic or necrotic cell death. In both species the epithelial cells exhibited all of the characteristics of apoptosis, including surface blebbing, shrinkage and fragmentation of the cells, condensation of chromatin, and indentation and fragmentation of nuclei. Cytoplasmic organelles remained morphologically intact, and the cytoplasm maintained normal or increased staining density. Also, the epithelial cells and cell fragments were phagocytosed by the adjacent trophoblast cells. The epithelial cells did not exhibit the characteristics of necrotic cell death, such as swollen cells and mitochondria, damaged surface membranes, and disintegrated cytoplasmic organelles. We conclude that uterine epithelial cells surrounding mouse and rat embryos during implantation undergo apoptotic cell death leading to their phagocytosis by trophoblast cells.

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice

“…However, unlike previous observations in Klf5 null mice, 5 these retained epithelial layers in the Rac1 null implantation chamber is not due to a reduced Cox2 expression. Because the disintegration of epithelial cells lining the implantation chamber is due to apoptosis in response to the invading blastocyst during normal pregnancy, 14 our findings suggested an intrinsic defect of Rac1 null epithelium undergoing apoptotic cell death after embryo-uterine attachment, highlighting the necessity of epithelial integrity for the initiation and progression of implantation. In fact, it has been reported that Rac1 is required for apoptotic cell clearance in bronchial epithelial cells and cell death in mammary gland epithelium.…”

“…14 There is early evidence that Caspase 3 is an executor of uterine epithelial apoptotic death and loss of Klf5 in mice leads to impaired epithelial cell elimination at postimplantation. 5,15 However, it remained largely elusive regarding the underlying mechanisms governing luminal epithelial cell death after blastocyst-uterus attachment.…”

The Expression and Possible Roles of Chemokine CXCL11 and Its Receptor CXCR3 in the Human Endometrium

“…Cell death, especially apoptosis, of endometrial epithelial cells occurs in implantation sites not only in mice (43), rats (44), and hamsters (45), but also in humans (3,46). Embryo-induced apoptosis of epithelial cells is an important mechanism for invading the luminal epithelium and breaching the epithelial barrier; the immediate consequence is that the trophoectoderm come in direct contact with the basement membrane and, then, stromal invasion can proceed (3).…”

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

“…One developmental process likely to contribute such high levels of extracellular AMP is cell death (Pearson and Gordon, 1979;Gordon, 1986;Papadimitriou et al, 1991). This process has been described in the uterine epithelium (El-Shershaby and Hinchliffe, 1975;Parr and Parr, 1987), primary decidua (Welsh and Enders, 1987;Parr and Parr, 19891, and secondary decidua (Welsh and Enders, 1985;Katz and Abrahamsohn, 1987) during implantation chamber morphogenesis in rodents. Adenosine production by 5'-NT would, by this model, accompany the progression of cell death a t the uterine-embryo interface.…”