The development of the endometrium during the first half of the menstrual cycle—the proliferative phase—is induced by estrogen from the maturing follicle, and its full functional differentiation occurs during the second half of the cycle under the influence of progesterone, and some estrogen, from the corpus luteum. It is likely that the development of the uterine microvasculature occurs in response to the same two hormones. Although endothelial cells have been reported to express low levels of estrogen and progesterone receptors, it is unlikely that they mediate the steroid-induced angiogenesis. Rather, the growth and differentiation is induced by paracrine angiogenic factors, such as vascular endothelial growth factor (VEGF), synthesized by the epithelial cells or stromal fibroblasts in response to estrogen and/or progesterone (and possibly by hypoxia as a result of increased tissue metabolism leading to oxygen demand exceeding supply). Treatment of immature rodents with estrogen induces a very rapid upregulation of VEGF expression in the uterus . Progesterone has also been shown to influence VEGF expression in several studies, and may especially induce its stromal production. As shown in Figure 4, the endometrial vessels are richly endowed with VEGF receptors.
Perhaps the best study to date of VEGF expression in the endometrium in relation to the vascular remodeling is that of Nayak and Brenner , in rhesus monkeys, a menstruating species. They observed a marked increase in VEGF expression in the proliferating epithelial cells during restoration of the luminal epithelium. This was matched by an increase in VEGF receptor expression in the underlying small vessels. This implicates VEGF in the repair of the endometrial microvasculature during postmenstrual healing. Hypoxia and the numerous cytokines and growth factors linked to wound healing could drive VEGF expression during this phase. Following reconstruction of the luminal epithelium, during the midproliferative stage of the menstrual cycle, there was a major peak in blood vessel growth (i.e., endothelial cell proliferation). This coincides with the rise in estrogen production by the preovulatory follicle and a peak in stromal VEGF expression. Endothelial cell labeling and VEGF expression were lower during the progesterone-dominated, secretory phase, but could still contribute to the continued lengthening of the larger feed arteries, which causes them to coil (hence, the origin of the term "spiral arteries"), as well as the final elaboration of the glandular and luminal subepithelial capillary complexes. Finally, there was an increase in VEGF expression in the glandular epithelial cells during the late secretory phase. This would be predicted to increase the permeability of the paraglandular capillaries, thereby enhancing glandular secretory capabilities.
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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.