Ovarian epithelium and cervix anatomy and function

Remember that this system is dynamic. The histology reflects this feature, so there is not one view of these organs, but a cycling continuum.

Overview of the ovary: location, gross structure and surface epithelium

The ovaries are paired organs situated on either side of the uterus. They are attached on one edge, the hilus, to the broad ligament of the uterus by a fold of peritoneum, the mesovarium. Using slide 239, examine the overall topography of the ovary and note the numerous vessels which enter it via the broad ligament. The ovaries are the female gonads. The gamete they produce is called an oocyte. The ovaries are located within the pelvic cavity, and are supported by the mesovarium, an extension of the peritoneum that connects the ovaries to the broad ligament. Each ovary, which is approximately 2 cm wide, 3 cm long, and 1 cm thick, lies between the uterus and the lateral pelvic walls. The surface of the ovary is covered with a simple squamous epithelium. The ovary comprises an outer covering of cuboidal epithelium called the ovarian surface epithelium that is superficial to a dense connective tissue covering called the tunica albuginea.

The ovary, when viewed in cross section, is composed of two layers: an inner medulla and an outer cortex. The inner medulla (present in most slides) is highly vascular and composed of a loose connective tissue core. The medulla is composed of loose connective tissue rich in lymphatic vessels, capillaries, and nerves. The cortex is composed of a compact bed of connective tissue containing numerous ovarian follicles. Examine the outer cortex of the ovary which is composed of stroma and numerous follicles in various stages of development. The cortex also contains many oocytes (300,000-400,000 at birth) embedded in this cortical stroma. Examine the stroma of the cortex in slide 239 and note the whorls of closely-packed, spindle-shaped fibroblasts. The inner ovarian medulla is the site of blood vessels, lymph vessels, and the nerves of the ovary.

Follicles and stages of folliculogenesis (histologic features)

Ovarian follicles are oocytes and their supporting cells. They grow and develop in a process called folliculogenesis, which typically leads to ovulation of one follicle approximately every 28 days, along with death to multiple other follicles. Folliculogenesis begins with follicles in a resting state. These small primordial follicles are present in newborn females and are the prevailing follicle type in the adult ovary. Primordial follicles are the most numerous ovarian follicles. They are the most superficial follicles, and are in a stage of resting meiotic prophase. Primordial follicles consist of a large oocyte surrounded by a layer of flattened follicular cells. Primary follicles consist of a large oocyte surrounded by a layer of cuboidal follicular cells. These follicular cells proliferate to form a loose multilayer, the granulosa cell layer. A rim of neutral glycoprotein, the zona pellucida (clear zone), surrounds the oocyte separating it from the surrounding granulosa cells.

Secondary follicles show that between the stratified granulosa cells there are large lacunae that coalesce to form the follicular antrum. The stromal cells surrounding the follicle have differentiated to form an inner layer (theca interna) of plump cells that secrete steroid precursors and an outer layer (theca externa) composed of concentrically arranged stromal cells that provide support for the developing follicle. With continued development, the follicle becomes a Graafian or ovulatory follicle. The granulosa zone now consists of many layers of cuboidal follicular epithelial cells located at the periphery of the large, well-formed follicular antrum. The oocyte has attained its full size, is located eccentrically within the follicle in a small hillock, the cumulus oophorus which protrudes into the antrum. The zona pellucida is surrounded by a continuous layer of follicular cells, the corona radiata. The theca interna is separated from the granulosa cells by a distinct basement membrane. Theca externa cells are densely packed, spindle-shaped cells which blend with the theca interna cells and with the surrounding stroma.

Because the contents of only one follicle are usually ovulated at a time in humans, other follicles which have been stimulated to develop must degenerate, or undergo atresia. Atresia is not limited to mature follicles, but may begin at any stage in follicular development. Early atretic alterations include clumping of the nuclear chromatin (pyknosis) and shrinkage and lysis of the cytoplasm of the oocyte, granulosa or follicular cells. Examine the pyknotic granulosa cells, which are sloughed into the follicular antrum. The basement membrane that separates the granulosa cells from the theca interna may also thicken considerably to form a so-called “glassy membrane.”

Corpus luteum and corpus albicans

After ovulation, the follicle which housed the ovum collapses and becomes highly infolded and invaded by vessels, forming the corpus luteum (yellow body). Examine slide 236a and observe that the corpus luteum appears pale and very folded. If the egg is fertilized and implants, the corpus luteum enlarges to become the corpus luteum of pregnancy. Examine the inner granulosa lutein cells (formed from the remaining granulosa cells) and the outer theca lutein cells which come from the remaining theca interna cells. Both cell types are polyhedral and filled with lipid droplets and have centrally located nuclei. The theca lutein cells are, however, considerably smaller, more darkly staining and have fewer lipid filled vacuoles than the granulosa lutein cells. Granulosa lutein cells contain a pigment, lipochrome, which produces the yellowish color of the corpus luteum in an unfixed ovary.

If the egg is not fertilized, the corpus luteum degenerates, and is gradually infiltrated with collagen and a few (if any) fibroblasts, forming the corpus albicans (white body). The corpus albicans is also formed during the later half of pregnancy when the placenta takes over steroid secretion from the corpus luteum.

Ovarian cycle, hormonal control and ovulation

The ovarian cycle is a set of predictable changes in oocytes and ovarian follicles. During the reproductive years, it is a roughly 28-day cycle that can be correlated with, but is not the same as, the menstrual cycle. Gametogenesis in females is called oogenesis. The process begins with the ovarian stem cells, or oogonia. Oogonia are formed during fetal development, and divide via mitosis. Unlike spermatogonia, however, oogonia form primary oocytes in the fetal ovary prior to birth. These primary oocytes are then arrested in this stage of meiosis I, only to resume it years later, beginning at puberty and continuing until near menopause.

As in males, the hypothalamus produces GnRH, a hormone that signals the anterior pituitary gland to produce the gonadotropins FSH and LH. FSH stimulates the follicles to grow, and the five or six tertiary follicles expand in diameter. The release of LH also stimulates the granulosa and theca cells of the follicles to produce the sex steroid hormone estradiol. The more granulosa and theca cells a follicle has, the more estrogen it will produce. Following a classic negative feedback loop, high concentrations of estrogen will stimulate the hypothalamus and pituitary to reduce the production of GnRH, LH, and FSH. This decline in FSH leads most follicles to undergo atresia and typically only one follicle, the dominant follicle, will survive.

When the dominant follicle produces very high estrogen concentrations, these trigger the anterior pituitary to secrete a large burst of LH and FSH (the LH surge) that leads to ovulation of the dominant follicle. The LH surge induces many changes in the dominant follicle, including stimulating the resumption of meiosis of the primary oocyte to a secondary oocyte and triggering proteases to break down structural proteins in the ovary wall, resulting in expulsion of the oocyte surrounded by granulosa cells into the peritoneal cavity. The surge of LH also stimulates luteinization, transforming the collapsed follicle into the corpus luteum which produces large amounts of steroid hormones.

Oviduct (fallopian tube): infundibulum, fimbriae, mucosa and muscularis

The oviduct conducts the ovulated egg from the peritoneal cavity to the uterus over a period of approximately three days, during which fertilization and segmentation of the zygote occurs. Examine its open end near the ovary, the infundibulum, and note the funneled shape and fimbriae. At low magnification note the general features of the ovary at the bottom of the section: the wide outer cortical region containing follicles, the central medulla, and the hilus (on the left). Next examine the infundibulum of the oviduct near the top of this section. Observe the extensive folding of its surface and the presence of fimbriae that extend toward the ovary and are sectioned at various angles. What is the function of these fimbriae? When an ovary releases an egg, fluid and the fimbriae propel it toward the fallopian tube opening. Once inside, the cilia move the egg toward the uterus.

Find the three layers of the oviduct wall, mucosa, muscularis, and serosa. Focus on identifying the ciliated and secretory (“peg”) cells of the mucosal epithelium. Note the inner circular and outer longitudinal smooth muscle layers in the muscularis, as well as the simple squamous mesothelium covering the serosa. Observe the major structural differences between the isthmus and the infundibulum of the oviduct; the isthmus has a thicker muscular wall and less elaborate mucosal folding than the infundibulum.

Uterus and endometrium: layers, cyclical changes and pregnancy-related transformation

At low power identify the different layers of the uterus (endometrium, myometrium and perimetrium). The uterus is a fibromuscular organ that can be divided into the upper muscular uterine corpus and the lower fibrous cervix. The endometrial cavity lies within the uterine corpus and is surrounded by a thick, muscular wall. The endometrium lines the uterine cavity and is considered to have three layers: the pars basalis, the zona spongiosa, and the superficial zona compacta. The straight branches of the radial arteries of the uterus terminate in capillaries in the basal layer, while the spiral or coiled branches penetrate to the surface epithelium, where they give rise to superficial capillaries. The endometrium varies considerably in thickness and gland morphology during the menstrual cycle.

In comparing the proliferative and secretory phases note the thickness of the endometrium (thicker in the secretory phase) and the shapes of the glands (more coiled or “corkscrew” regions in the secretory). In the proliferative phase the endometrial glands are relatively straight and lined with columnar epithelium and occasional mitoses can be seen. The stroma is a highly cellular connective tissue. With the implantation of a zygote into the uterus, cells from the embryonic trophoblast invade the uterine mucosa, secretions from these cells coalesce to form lacunae in the endometrium, which is now termed the decidua. These spaces also contain maternal blood.

The trophoblast rapidly invades the decidua forming primary chorionic villi that contain only trophoblast cells (outer syncytiotrophoblast and inner cytotrophoblast). Mesenchyme and blood vessels form the core of the secondary villi. The syncytiotrophoblast cells are more eosinophilic and have smaller nuclei; they result from the fusion of many cells and thus have many nuclei per cell and no discernable lateral boundaries. Cytotrophoblast cells are clearly demarcated, have a single, large nucleus and basophilic cytoplasm. Syncytiotrophoblast cells that are bathed in maternal blood have apical surfaces specialized for absorption (microvilli), pinocytosis, and exocytosis and an appearance typical of secretory cells.

Cervix: anatomy, epithelial zones, glands and the transformation zone

The cervix, which protrudes into the vagina, is generally 2-3 cm long. The intravaginal portion of the cervix, known as the portio vaginalis, ordinarily is covered with nonkeratinizing squamous epithelium with a number of mucus-secreting glands. The external os is the opening of the cervix within the vagina. Above the external os lies the fusiform endocervical canal, approximately 2 cm long and lined with columnar epithelium and endocervical glands. The intersection where the squamous epithelium of the exocervix and columnar epithelium of the endocervical canal meet, the squamocolumnar junction, is geographically variable and dependent on hormonal stimulation. It is this dynamic interface, the transformation zone, that is most vulnerable to the development of squamous neoplasia.

First, scan at low power the cervix on the lower edge of the section and observe the cervical glands in the endometrium. Notice that the large, branched glands differ in shape from the glands in most of the uterus. The endocervical canal in the nullipara is lined by mucosa arranged in a series of folds. A vertical fold is present on the anterior and posterior cervical walls; from these, oblique folds radiate. These folds have been called the arbor vitae uteri or plicae palmatae. The glands of the cervix are definitely evident. There are no glands underlying the squamous epithelium of the vagina.

The cervix has several important functions: producing mucus that helps regulate sperm entry and protects the uterus from bacteria, allowing menstrual blood and other fluids to drain through its small opening, and undergoing dilation during childbirth. The squamocolumnar junction and the transformation zone change position with age and hormonal status; in early childhood, during pregnancy, or with oral contraceptive use, columnar epithelium may extend onto the exocervix (eversion or ectopy), while after menopause the transformation zone usually recedes into the endocervical canal.

Vagina and adjacent epithelium: structure and histology

The vagina connects the female reproductive system to the exterior of the body. At low magnification, note its three-layered structure: the mucosal lining, smooth muscle layer, and outer adventitial layer. The walls of the vagina are lined with an outer, fibrous adventitia; a middle layer of smooth muscle; and an inner layer of stratified squamous epithelium that rests on a lamina propria. The vaginal epithelium forms transverse folds, called rugae, which increase surface area and allow for stretching. The outer layers of these epithelial cells are filled with glycogen giving them an empty appearance, characteristic of this vaginal epithelium.

The connective tissue of the thick lamina propria contains many elastic and collagen fibers throughout and many small veins in the deeper region. The subjacent smooth muscle layers are arranged in poorly defined inner circular and predominant outer longitudinal layers. The connective tissue of the outer adventitial layer also contains many elastic fibers, thus contributing to the overall distensibility of this region. Also evident in the adventitia in both H&E and trichrome-stained sections are parasympathetic ganglia that innervate the erectile tissue.

Clinical and pathological notes

Ovarian cancer is the second most common gynecologic cancer, causing more deaths than any other cancer of the female reproductive system. Ovarian cancer is the result of abnormal and uncontrollable cellular growth within one or both of the ovaries. In the early stages of development most individuals exhibit no signs or symptoms of the disease or, if they do, the signs and symptoms are often blamed on other common conditions. Germ cell tumors develop from the ova contained within the follicle of the ovary.

This slide contains a biopsy of the uterus from a 38-year-old woman who presented with irregular menstruation and intense, episodic uterine cramping. Grossly, the myometrium was distorted by numerous circumscribed nodules ranging in size from 2 to 6 centimeters. Note the structure of the surrounding normal myometrium -- interlacing bundles of spindle-shaped cells organized into fascicles. You will see that the neoplasm is also composed of interlacing bundles of spindle shaped cells.

Selected histology-slide observations and correlations

1. At low magnification note the general features of the ovary at the bottom of the section: the wide outer cortical region containing follicles, the central medulla, and the hilus (on the left).
2. Observe the extensive folding of the infundibulum surface and the presence of fimbriae that extend toward the ovary and are sectioned at various angles.
3. Find the three layers of the oviduct wall, mucosa, muscularis, and serosa, and identify the ciliated and secretory (“peg”) cells of the mucosal epithelium.
4. In the uterus compare proliferative and secretory phases: endometrium is thicker in the secretory phase and glands are more coiled or “corkscrew” shaped in the secretory.
5. In the cervix observe large, branched cervical glands that differ from uterine glands and recognize the non-keratinized stratified squamous epithelium of the vagina at the boundary regions.
6. With implantation, trophoblast invasion forms lacunae and primary chorionic villi; syncytiotrophoblast and cytotrophoblast have distinct morphologies and roles.

Identify as specifically as possible the organ shown in a given uterine slide and provide features: the endometrium, myometrium and perimetrium can be identified; endometrial glands and stroma demonstrate phase-specific morphology (straight glands and dense stroma in late proliferative; thickened, coiled glands in secretory); cervical glands are large and branched and differ from uterine glands; vaginal epithelium is non-keratinized stratified squamous with glycogen-filled superficial cells.

tags: #ovarian #epithelium #maternicni #vrat