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.
Fallopian tube
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).
Uterus
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.
