Structural Changes in the Endometrial Microvasculature Associated with Implantation

The initial structural change in the endometrial microvas-culature upon the penetration of the implanting embryo into the stroma is actually the establishment of a totally avascu-lar zone, called the primary decidual zone, immediately around it. Whether this involves a displacement of stromal vessels away from the embryo by decidualizing stromal fibroblasts or the regression of vessels (or a combination of the two processes) is unclear. Studies have demonstrated that this dense zone of decidual cells is an effective barrier to the diffusion of proteins larger than about 45,000MW to the embryo. Thus, it probably serves a protective function, preventing harmful immunoglobulins and immune cells from reaching the embryo, which is immunologically foreign, until it establishes its own protective layers, while still permitting the passage of oxygen and essential nutrients from capillaries immediately outside the zone. Outside this zone, continuous growth and remodeling of the capillary bed and associated arteries and veins continues to support and accommodate the invading and growing embryo [16].

An increase in endometrial microvascular permeability and edema are critical for implantation. In rodents, this increase is triggered by the brief spike in estrogen on the fourth day after mating. The increase in permeability makes it possible to readily visualize implantation sites in rodents with the naked eye following intravenous injection of blue protein dyes [11]. Marked edema also occurs peripheral to the implanting blastocyst in primates [17]. Increased permeability immediately precedes decidualization, in which it is thought to play a causal role. Edema is probably critical for implantation for several reasons in addition to the general role it plays in the promotion of cell growth, tissue remodeling, and angiogenesis, as described earlier. The swelling of the uterine walls clasps the blastocyst in the uterine lumen, bringing it in intimate association with the epithelium. This may trigger the breakdown of the latter, placing the blasto-cyst into direct contact with the endometrial stroma, where it further enhances local microvascular permeability and the decidualization process. In species with multiple young, such as rats and mice, edema at the implantation sites, and not in adjacent portions of the uterus, has also been proposed to cause differential uterine elongation and growth, thereby leading to even spacing between embryos, which is likely critical as they grow to full-term fetuses.

The implantation-related increase in permeability is again VEGF dependent. Several studies have shown that VEGF and its receptors are expressed immediately around the implanting blastocyst, and we have demonstrated that administration of an antibody to VEGF to mice on the fourth day after mating completely blocks implantation [10].

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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