Consequently, it is subdivided only into the early, middle, and late proliferative phases. For clinical purposes this subdivision suffices, since the relevant functional changes become evident only in the secretory phase. Early Proliferative Phase In the early proliferative phase Figs. The glandular epithelial cells are low columnar cells; they contain small, rounded, or oval-shaped chromatin-dense nuclei in a sparse cytoplasm.
The stromal cells are poorly differentiated and of equal size with small, dense nuclei in a scanty cytoplasm.
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Nucleoli are inconspicuous and mitoses are very rare. The cells are surrounded by a firm reticulin network. Spiral arterioles are undeveloped. The surface epithelium is flat and still regenerating. Distinction is possible only by precise statement of the day of the menstrual cycle and by recording in anovulatory cycles the basal body temperature curve.
Distinction on morphologic grounds alone is not possible. Midproliferative Phase In the midproliferative phase Figs.
The glandular epithelial cells are tall columnar cells and contain slightly enlarged oval-shaped, chromatin-rich nuclei in a dense, sparse cytoplasm rich in RNA. Nucleoli are prominent, and mitoses frequent. The spindle-shaped stromal cells are still poorly differentiated, but rich in DNA and RNA with occasional mitoses and separated by interstitial edema Harkin Spiral arterioles are not seen. The surface epithelium has increased in height and is now low columnar.
Clinical Possibilities. Late Proliferative Phase In the late proliferative phase Figs. The nuclei are enlarged still further, rich in DNA, and more elongated or oval shaped. Nucleoli are quite prominent, and mitoses are frequent.
The cytoplasm is still sparse and poorly differentiated, but rich in RNA. Stromal mitoses are frequent. The cells are still of uniform size and without signs of differentiation. The stromal edema has subsided. The reticulin network is dense. Spiral arterioles are still absent. The general height may be slightly lower than that of the midproliferative phase due to decrease of edema.
The surface epithelium is distinctly columnar. If the deviation from this limit is more than 2 days, a functional disturbance should be diagnosed. Because the glandular epithelium reacts more quickly to the influence of progesterone than do the stromal cells, histologic dating is based mainly on the changes of the glandular epithelium during the first week of the secretory phase and on the changes in the stromal cells during the second week.
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The histologic signs induced in the endometrium by hormones are never uniform. Differences are related to various factors, such as local blood supply, cellular nutrition, and various metabolic factors, e. For dating the endometrium, those regions showing the most advanced changes are relevant. The first day after ovulation is morphologically mute and therefore designated as interphase because it takes 36—48 h before changes induced by the progesterone secretion can be detected with certainty under the light microscope.
Sporadic vacuoles appear in some of the glandular cells even immediately before ovulation, but are unreliable as definite signs of ovulation.
They have pushed the nucleus towards the lumen. At their formation the previously pseudostratified appearance of the nuclei disappears; the nuclei again form a single row. They are still 14 Fig. With this new arrangement of the nuclei, the glands become increasingly tortuous and enlarge their surfaces at the glandular lumen. Basal vacuoles, however, fail to appear in the superficial portions of the gland where it merges with the surface epithelium Fig. The surface epithelium of the endometrium remains tall, with no signs of basal secretion.
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No remarkable changes can be detected in the stroma when compared with those of the late proliferative phase. Based on morphology, ovulation can be confirmed when distinct basal vacuoles have appeared in most of the glandular epithelial cells. The third day after ovulation Figs. This secretion has pushed all the nuclei toward the apical end of the cell, where they form a uniform row around the lumen.
The nuclei remain dense and rich in chromatin, and only a few mitoses are seen.
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The cytoplasm still contains abundant RNA. On the fourth day after ovulation Figs. A few of them start to return to the base of their cells, while tiny amounts of glycogen move towards the lumen. A small rim of mucopolysaccharides can be observed at the luminal margin of the epithelial cells, but only with special stains Fig. This rim is characteristic of the fourth day after ovulation.
On the fifth day after ovulation Fig. The glycogen has moved or is moving towards the lumen of the cells on both sides of the nucleus, Fig. The movement of the glycogen can best be followed with a PAS stain.
Since the nuclei are now vesicular and pale upon staining, they can be easily distinguished from the dense, elongated, basally located nuclei of the cells before the glycogen vacuoles appeared. The nucleoli have now become greatly enlarged. The sixth day after ovulation Figs. All epithelial nuclei have now returned to the base of the cells. The glandular cells have decreased in height and their luminal margins appear shredded and hazy due to the excessive apocrine secretion. The RNA content of the cytoplasm is decreased. On the seventh day after ovulation Figs.
As a sign of active secretion, the apical ends of the glandular cells appear frayed. No new glycogen is secreted from the cell base. The first stromal reaction after ovulation has occurred and becomes apparent on this day; there is a patchy reaccumulation of stromal edema. On the eighth day after ovulation Figs.
It is now diffuse and quite intense, with the stromal cells widely separated from one another. These are still spindle shaped, but somewhat enlarged. Their differentiation becomes even more apparent from this day on Fig. The overall height of the endometrium has increased. The glandular lumen is filled with green-staining glycogen. Groups of spiral arterioles are now prominent. The stromal cells surrounding these spiral arterioles grow larger and more rounded. Their nuclei enlarge and appear less chromatin dense. Their cytoplasm is increased in amount and in RNA content. The stromal cells which are further away from the arterioles remain only slightly enlarged.
Glandular secretion has ceased, but remnants of secreted substance may be found in the glandular lumina. On the tenth day after ovulation Figs.