Microscopic Anatomy Of The Female Reproductive Tract
The ovary has two distinct functions: germ cell production and steroid hormone biosynthesis. Germ cell support occurs in microscopic structures known as ovarian follicles. Resting follicles each contain a primitive or primordial oocyte surrounded by a single layer of cells, the granulosa cells. Surrounding the granulosa cells are a collar of cells known as theca cells. Theca cells produce androgens that are then converted to estrogens by the granulosa cells (Chapter 2). Steroid hormones produced by the ovary act within the follicle to support the developing oocyte and outside the ovary on target tissues.
The human ovary contains about 2 million oocytes at birth but only 100 000 at puberty. The number of oocytes continues to decrease throughout a woman’s reproductive lifespan. This decrease occurs because mitosis of the primitive oogonia stops midway through fetal life and does not resume. At the time mitosis stops, the newly formed oocytes enter into the prophase of the first meiotic division. They will remain in meiotic prophase until either they are stimulated to mature for ovulation or they degenerate in a process called atresia.
The primordial follicles are scattered just beneath the connective tissue capsule covering the ovary (Fig. 10.1). This superficial position permits ovulation into the abdominal cavity. The earliest signs of follicular growth are: (i) an increase in size of the oocyte; (ii) a change in the shape of the surrounding granulosa cells from flat to cuboidal; (iii) an increase in granulosa cell number; and (iv) the appearance of a zona pellucida around the oocyte. The zona pellucida is a sphere of gelatinous protein matrix immediately surrounding the oocyte. Once growth of the granulosa cells has produced three to four layers of cells, fluid begins to accumulate between the cells. This fluid resembles blood plasma and contains high concentrations of several protein and steroid hormones. When this follicular fluid accumulates around the oocyte, the follicle is known as a Graafian follicle and is approaching ovulation. Although as many as 20 follicles begin to mature in each wave of recruitment, typically only one successfully ovulates.
Ovulation involves expulsion of the egg through a thinned-out area known as the stigma. Stigmata can be seen with the naked eye as “blisters” on the surface of the ovary. Once the oocyte is released, the follicle collapses and the granulosa cells proliferate to fill the space left by the oocyte and its associated follicular fluid. They undergo transformation into plump, endocrinologically active cells known as lutein cells. These lutein cells produce a yellow pigment and the structure containing these cells is appropriately called the corpus luteum, or yellow body. During corpus luteum formation, blood vessels penetrate the follicular basement membrane.
The lumen of the fallopian tube is covered by a columnar epithelium with long cilia on the surface of many of the cells. The cilia constantly beat toward the uterus, a function that facilitates movement of the nonmotile zygote toward the uterine cavity for implantation. When cilia are injured or incapable of movement, an embryo may inappropriately implant within the fallopian tube itself (ectopic pregnancy).
The vast majority of the uterine wall is composed of smooth muscle, called myometrium. The smooth muscle cells of the myometrium (myocytes) are attached by gap junctions, allowing rapid communication among neighboring cells and coordinated movement of the entire muscle mass. The uterus must be capable of enormous growth during pregnancy. This is accomplished by hypertrophy of the myocytes and by recruitment of new myocytes from stem cells residing within the myometrial connective tissue.
The cavity of the uterus is lined by a glandular epithelium, the endometrium. The endometrium is both an endocrine target organ and a gland. Under the influence of cyclic hormone production by the ovary, the endometrium undergoes striking microscopic changes in its glandular structure and function (Fig. 10.2). During the preovulatory phase of the menstrual cycle, the epithelial cells on the surface of the endometrium proliferate profusely under the influence of estrogen. The glands proliferate and elongate deep into the subepithelial layer known as the endometrial stroma. Small muscular arteries known as spiral arteries grow inward from the basal layer of the endometrium between the elongating glands. The hallmark of the proliferative endometrium is frequent mitoses in the epithelium. Immediately prior to ovulation, the endometrial glands are maximally elongated and markedly coiled. With ovulation, the hormonal environment within the uterus becomes even more progesterone-dominant. In response to the change, mitosis ceases in the glandular epithelium and the cells form a single columnar layer within the glands. Within 2 days of ovulation, small subnuclear vacuoles form in the cytoplasm of the columnar cells. These secretory vacuoles are rich in glycogen and lipid and, by 4 days after ovulation, they migrate to the luminal side of the cells. Over the next 2 days, the vacuoles discharge their contents into the glandular lumens, leaving borders of the glandular cells frayed in appearance. This activity is the basis for the term secretory endometrium, which is used to describe the postovulatory endometrial changes.
Concurrent with these glandular changes are marked alterations in the endometrial stromal cells. With ovulation, stromal cells enlarge and acquire a foamy appearance indicative of increased metabolism. These cells become very eosinophilic and are known as decidual cells. Decidualization of the endometrium begins around the elongated and coiled spiral arteries. Decidualization then spreads under the surface epithelium and glands by 10 days after ovulation.
If implantation does not occur in a given menstrual cycle, progesterone production by the corpus luteum stops by day 13–14 postovulation. The endometrium undergoes ischemic necrosis and sloughs off, shed as menstrual debris. If pregnancy occurs, the extended lifespan of the corpus luteum will prolong progesterone production and decidualization of the stroma continues. The endometrial stroma is an important source of several peptides in pregnancy, including prolactin, insulin-like growth factor binding protein 1 (IGFBP-1) and parathyroid hormone-related peptide (PTHrP).
The hormone-driven histologic changes in the endometrium are so predictable that they can be used to document ovulation and its timing.
Cervix and vagina
The cervix is composed largely of connective tissue. This is covered by a layer of mucus secreting glandular epithelium inside the cervical canal (endocervix) and a stratified squamous epithelium on the portion of the cervix visible within the vagina (ectocervix). The transition between the glandular and squamous epithelium is known as the transformation zone. The transformation zone typically occurs very near the external os of the cervix. The zone is important in that it is a common site of dysplastic changes that can become malignant. The vagina is covered with squamous epithelium.