This article reviews the main events of embryo-implantation and decidualization in rodents. In common laboratory rodents the embryo attaches to the uterine epithelial lining, usually on days 4 to 6 of pregnancy. A progressive degree of proximity between trophoblast and epithelium occurs until the epithelial cells undergo apoptosis and detach from the basement membrane. During the attachment stage, the spindle-shaped connective tissue cells that underlie the epithelium next to the embryos transform into polyhedral and closely packed decidual cells. Following the epithelial detachment and the breaching of the basement membrane the embryo is thus in direct contact with decidual cells. These cells accumulate organelles associated with synthesis of macro-molecules, intermediate filaments, and eventually lipid droplets and glycogen. Another remarkable feature of decidual cells is the establishment of gap and adherens intercellular junctions. Differentiation of fibroblasts into decidual cells advances antimesometrially and mesometrially, creating in the endometrium several regions of cells with different morphology. The whole phenomenon of decidualization which is normally triggered by the embryo can be artificially induced in pseudo-pregnant or hormonally-prepared animals with the use of diverse stimuli. The uterine epithelium is probably responsible for the transduction of the initial stimulus. Prostaglandins have been shown to be important in the induction of decidualization. More recently other substances such as leukotrienes, platelet-activating factor (PAF), and transforming growth factor (TGF) have been thought to play a role in induction. Much evidence points to prostaglandin production by the decidual cells. New proteins such as a luteotropic factor, desmin, and other molecules were shown to be produced after rat stromal cells undergo decidual transformation. The extracellular matrix of the mouse decidua contains very thick collagen fibrils. Mouse decidual cells are also very active in phagocytosing the thick fibrils, contributing to the remodeling and involution of the decidua that accompanies embryonic growth. Radioautographic data indicates that mouse decidual cells produce and secrete collagen and sulfated proteoglycans.
An ultrastructural study of the features and distribution of collagen fibrils was performed in the endometrium of virgin and pregnant (2nd to 11th day) mice. Collagen-containing structures were observed in the cytoplasm of fibroblasts on the 2nd day of pregnancy. Treatment of tissues with lanthanum nitrate established that these structures were intracytoplasmic. Their association with lysosome-like bodies suggested the occurrence of intracellular digestion of collagen, probably connected with remodeling of the endometrial stroma prior to decidualization. On the 4th day of pregnancy, very few collagen fibrils were present in the intercellular space. From the 6th day of pregnancy onwards, "thick" collagen fibrils were observed between decidual cells. The diameter of these fibrils measured up to 300 nm whereas the fibrils present in the endometrium of virgin mice measured 40-68 nm.
Remodelling of the extracellular matrix (ECM) occurs during decidualization of the endometrium in mice. Previously we have documented the appearance of large-diameter collagen fibrils around mature decidual cells between day 5 and day 7 of pregnancy. Proteoglycans are important in the regulation of collagen fibrillogenesis, and the present study analysed four members (decorin, biglycan, lumican and fibromodulin) of the family of small leucine-rich proteoglycans (SLRPs) in the uterus from day 1 to day 7 of pregnancy. Decorin was present together with lesser amounts of lumican in the stroma before the onset of decidualization, whereas biglycan and fibromodulin were almost absent. Biglycan and, less significantly, lumican were expressed in decidualized regions of the endometrium, but decorin was absent. Fibromodulin was weakly expressed in the non-decidualized stroma, but only after implantation. Decorin and lumican were strongly expressed in the undifferentiated interimplantation site stroma, whereas biglycan and fibromodulin were expressed only weakly. These results indicate that the SLRP profile of the uterine ECM alters with differentiation of endometrial stromal cells. The large decidual collagen fibrils are thought to arise by lateral association of smaller diameter fibrils. As decorin has been shown to inhibit lateral association of collagen fibrils, its disappearance between day 2 and day 5 of pregnancy may be a prerequisite for the formation of large fibrils in decidua in mice.
Involution of the antimesometrial decidua was analysed by electron microscopy on days 9, 10 and 11 of pregnancy in the mouse. During this period, the width of the antimesometrial decidua decreases considerably. Involution begins in the decidual cells situated closest to the embryo (internal decidua) and proceeds towards the myometrium. The cells of the internal decidua showed signs of deterioration characterized by accumulation of clumps of chromatin in the nuclei and dilation of the perinuclear cisterna and endoplasmic reticulum cisternae. Autophagosomes and heterophagosomes accumulated in the cytoplasm of these cells. Cells particularly strongly affected became spherical and were devoid of their plasma membrane. Some cells near the trophoblast as well as the mature decidual cells situated farther from the embryo showed a normal morphology. The trophoblastic cells established close contact with healthy decidual cells and engulfed fragments of disorganized decidual cells. It is suggested that the death of decidual cells is a type of programmed cell death and that it is not due to a direct lytic action by the trophoblast.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.