Cyclic Changes During the Menstrual Cycle

Cyclic changes of the endometrium during the menstrual cycle are represented by the proliferative, secretory, and menstrual phases

The menstrual cycle is a continuum of developmental stages in the functional layer of the endometrium. It is ultimately controlled by gonadotropins secreted by the pars dis-talis of the pituitary gland that regulate the steroid secretions of the ovary. The cycle normally repeats every 28 days, during which the endometrium passes through a sequence of morphologic and functional changes. It is convenient to describe the cycle as having three successive phases:

• Proliferative phase, occurring concurrently with follicular maturation and influenced by ovarian estrogen secretion

• Secretory phase, coinciding with the functional activity of the corpus luteum and primarily influenced by progesterone secretion

• Menstrual phase, commencing as hormone production by the ovary declines with the degeneration of the corpus luteum (see Fig. 22.14)

The phases are part of a continuous process; there is no abrupt change from one to the next.

The proliferative phase of the menstrual cycle is regulated by estrogens

At the end of the menstrual phase, the endometrium consists of a thin band of connective tissue, about 1 mm thick, containing the basal portions of the uterine glands and the lower portions of the spiral arteries (see Fig. 22.17). This layer is the stratum basale; the layer that was sloughed off was the stratum functionale. Under the influence of estrogens, the proliferative phase is initiated. Stromal, endothelial, and epithelial cells in the stratum basale proliferate rapidly, and the following changes can be seen:

• Epithelial cells in the basal portion of the glands reconstitute the glands and migrate to cover the denuded endometrial surface.

• Stromal cells proliferate and secrete collagen and ground substance.

• Spiral arteries lengthen as the endometrium is reestablished; these arteries are only slightly coiled and do not extend into the upper third of the endometrium.

The proliferative phase continues until 1 day after ovulation, which occurs at about day 14 of a 28-day cycle. At the end of this phase, the endometrium has reached a thickness of about 3 mm. The glands have narrow lumina and are relatively straight but have a slightly wavy appearance (Fig. 22.18a). Accumulations of glycogen are present in the basal portions of the epithelial cells. In routine his tologic preparations, extraction of the glycogen gives an empty appearance to the basal cytoplasm.

The secretory phase of the menstrual cycle is regulated by progesterone

Under the influence of progesterone, dramatic changes occur in the stratum functionale, beginning a day or two after ovulation. The endometrium becomes edematous and may eventually reach a thickness of 5 to 6 mm. The glands enlarge and become corkscrew shaped, and their lumina become sacculated as they fill with secretory products (Fig. 22.18b). The mucoid fluid produced by the gland epithelium is rich in nutrients, particularly glycogen, required to support development if implantation occurs. Mitoses are now rare. The growth seen at this stage results from hypertrophy of the epithelial cells, an increase in vascularity, and edema of the endometrium. The spiral arteries, however, lengthen and become more coiled. They extend nearly to the surface of the endometrium.

The sequential influence of estrogens and progesterone on the stromal cells enables their transformation into decidual cells. The stimulus for transformation is the implantation of the blastocyst. Large, pale cells rich in glycogen result from this transformation. Although the precise function of these cells is not known, it is clear that they provide a favorable environment for the nourishment of the embryo and that they create a specialized layer that facilitates the separation of the placenta from the uterine wall at the termination of pregnancy.

The menstrual phase results from a decline in the ovarian secretion of progesterone and estrogen

The corpus luteum actively produces hormones for about 10 days if fertilization does not occur. As hormone levels rapidly decline, changes occur in the blood supply to the stratum functionale. Initially, periodic contractions of the walls of the spiral arteries, lasting for several hours, cause the stratum functionale to become ischemic. The glands stop secreting, and the endometrium shrinks in height as the stroma becomes less edematous. After about 2 days, extended periods of arterial contraction, with only brief periods of blood flow, cause disruption of the surface epithelium and rupture of the blood vessels. When the spiral arteries close off, blood flows into the stratum basale but not into the stratum functionale. Blood, uterine fluid, and sloughing stromal and epithelial cells from the stratum functionale constitute the vaginal discharge. As patches of tissue separate from the endometrium, the torn ends of veins, arteries, and glands are exposed (Fig. 22.18c). The desquamation continues until only the stratum basale remains. Clotting of blood is inhibited during this period of menstrual flow. Arterial blood flow is restricted except for the brief periods of relaxation of the walls of the spiral arteries. Blood continually seeps from the open ends of the veins. The period of menstrual flow normally lasts about 5

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