Ovary, Uterus, and Vagina

Introduction

• The female reproductive system includes internal genital organs, external genital organs, and accessory glands.
• Internal genital organs, located within the pelvis, include the ovaries, uterine (fallopian) tubes, uterus, and vagina.
• External genital organs, collectively known as the vulva, include the mons pubis, labia majora, labia minora, clitoris, vestibule, and vaginal orifice.
• Accessory reproductive glands include the mammary glands, Skene’s (paraurethral) glands, and Bartholin’s (greater vestibular) glands. Temporary structures associated with pregnancy include the placenta and umbilical cord.
• The menstrual cycle consists of cyclic changes in the ovaries and uterus regulated by reproductive hormones.
• Menarche is the onset of menstruation and typically occurs between 9 and 14 years of age.
• Menopause marks the permanent cessation of menstrual cycles and usually occurs between 45 and 55 years of age.
• The average menstrual cycle lasts approximately 28–30 days, although normal variation exists among individuals.

Ovary

• The ovary is the female gonad and performs two essential functions:
  • Gametogenesis: Production and maturation of female gametes (oocytes).
  • Hormone secretion: Production of estrogens and progesterone, which regulate reproductive function and the menstrual cycle.
• Ovaries are paired, almond-shaped organs with a pinkish-white appearance.
• Each ovary is attached to the broad ligament and typically measures about 3 cm × 1.5 cm × 1 cm.

General Structure of Ovary

• Each ovary consists of the following components:

Germinal Epithelium

• The ovarian surface is covered by a single layer of simple cuboidal epithelium, traditionally called the germinal epithelium.
• Despite its name, this epithelium does not produce germ cells.
• Female germ cells originate from primordial germ cells that migrate from the yolk sac during embryonic development.
• The surface epithelium is continuous with the mesothelium of the peritoneum.

Tunica Albuginea

• Beneath the surface epithelium lies the tunica albuginea, a thin layer of dense connective tissue.
• This layer is considerably thinner than the tunica albuginea of the testis.

Cortex

• The cortex forms the outer functional region of the ovary, located beneath the tunica albuginea.
• It contains ovarian follicles at various stages of development embedded within a highly cellular stromal tissue.
• Cortical stroma gives rise to supporting follicular structures, including granulosa cells, theca interna, theca externa, corona radiata, and cumulus oophorus.
• The cortex also contains corpus luteum, corpus albicans, and atretic follicles.

Medulla

• The medulla occupies the central part of the ovary.
• It consists mainly of loose connective tissue containing numerous blood vessels, lymphatics, and nerve fibers.
• The hilum of the ovary serves as the entry and exit site for blood vessels and nerves.
• Histologically, the boundary between the cortex and medulla is not sharply defined.

Ovarian Follicles (Oogenesis)

• The ovarian cortex contains follicles at different stages of development, including primordial follicles, primary follicles, secondary follicles, Graafian follicles, corpus luteum, corpus albicans, and atretic follicles.

Oogonia

• During fetal life, primordial germ cells differentiate into oogonia.
• Oogonia undergo mitotic divisions and enlarge to form primary oocytes.
• Before birth, primary oocytes enter meiosis I and become arrested in the dictyotene (diplotene) stage of prophase I.
• This arrest is maintained until puberty by factors produced within the follicle.
• At birth, the ovaries contain several hundred thousand primary oocytes, but only about 400–500 are ovulated during reproductive life.
• From birth until puberty, most follicles remain dormant.

Primordial Follicle

• Primordial follicles are located immediately beneath the tunica albuginea.
• Each follicle contains:
  • A primary oocyte with a prominent nucleus and cytoplasmic organelles, including the Balbiani body.
  • A single layer of flattened follicular cells surrounding the oocyte.

Primary Follicle

• Growth of the primordial follicle produces a primary follicle.
• Follicular cells become cuboidal and proliferate to form the granulosa cell layer.
• The oocyte secretes the zona pellucida, a glycoprotein-rich layer that surrounds it and stains positively with PAS stain.
• Stromal cells differentiate into:
  • Theca interna, a vascular endocrine layer.
  • Theca externa, an outer connective tissue layer containing collagen fibers and smooth muscle cells.

Secondary Follicle

• Continued follicular growth leads to the formation of fluid-filled spaces among granulosa cells.
• These spaces merge to form the antrum, which contains liquor folliculi.
• The oocyte enlarges significantly, reaching approximately 120–125 μm in diameter.
• Granulosa cells surrounding the oocyte form the cumulus oophorus, which later gives rise to the corona radiata.
• Call–Exner bodies, small PAS-positive extracellular deposits rich in glycoproteins and hyaluronic acid, may be present between granulosa cells.

Graafian Follicle

• The Graafian follicle is the fully mature ovarian follicle and may exceed 10 mm in diameter.
• Just before ovulation, the primary oocyte completes meiosis I to form a secondary oocyte and the first polar body.
• The enlarged antrum occupies most of the follicle, while granulosa cells around the oocyte form the corona radiata.
• The mature follicle bulges from the ovarian surface before ovulation.
• Theca interna cells produce androgens, which are converted into estrogens by granulosa cells, supporting follicular growth and maturation.

Ovulation

• Ovulation is the release of a secondary oocyte from a mature Graafian follicle.
• The process is facilitated by:
  • Increased pressure from accumulating follicular fluid.
  • Proteolytic activity mediated by plasminogen activators, which weaken the follicular wall.
  • Prostaglandin-induced contraction of smooth muscle cells in the theca externa.
• A small avascular area called the stigma (macula pellucida) develops on the ovarian surface over the bulging follicle.
• Rupture at this site allows the secondary oocyte, surrounded by the corona radiata, to be released.
• The secondary oocyte remains viable for approximately 24 hours after ovulation.
• It is arrested in metaphase II of meiosis and completes meiosis only if fertilization occurs.

Corpus Luteum/Luteal Gland

• Following ovulation, the ruptured follicle collapses and transforms into the corpus luteum.
• Granulosa and theca interna cells enlarge and accumulate lipid pigments, giving the structure its characteristic yellow color.
• Two main cell types are present:
  • Granulosa lutein cells, which predominantly secrete progesterone.
  • Theca lutein cells, which mainly produce estrogens.

• The corpus luteum prepares the endometrium for possible implantation and supports early pregnancy if fertilization occurs.

Corpus Albicans

• In the absence of fertilization, the corpus luteum undergoes degeneration.
• Luteal cells regress and are gradually replaced by fibrous connective tissue, forming the corpus albicans.
• This scar-like structure eventually shrinks and becomes inconspicuous within the ovarian cortex.

Follicular Atresia

• Most ovarian follicles do not ovulate and instead undergo follicular atresia.
• Characteristic changes include:
  1. Apoptosis and degeneration of granulosa cells.
  2. Enlargement of theca interna cells.
  3. Removal of degenerating cells by macrophages.
  4. Replacement of follicular structures by connective tissue.
• A prominent feature of atretic follicles is the formation of a thick, wavy glassy (hyaline) membrane, produced by thickening of the basement membrane between granulosa and theca layers.

Fallopian Tube (Uterine Tubes)

• The fallopian tubes are paired muscular ducts that transport the oocyte from the ovary to the uterus and provide the usual site for fertilization.
• Each tube measures approximately 10–12 cm in length.

Parts of the Fallopian Tube

1. Infundibulum: Funnel-shaped lateral end bearing finger-like fimbriae that help capture the ovulated oocyte.
2. Ampulla: Longest and widest segment; the most common site of fertilization.
3. Isthmus: Narrow, thick-walled medial segment.
4. Uterine (intramural/interstitial) part: Traverses the uterine wall and opens into the uterine cavity.

Histology of Fallopian Tube

• Wall of fallopian tube shows three layers from inside outwards: Mucosa, muscle layer, and serosa.

Mucosa

• The mucosa forms numerous branching longitudinal folds that project into the lumen, especially in the ampulla.
• It is lined by simple columnar epithelium containing three cell types:
  • Ciliated cells: Propel the oocyte and tubal contents toward the uterus through coordinated ciliary movement.
  • Secretory (peg) cells: Produce nutritive fluid that supports sperm, oocytes, and early embryos and facilitates sperm capacitation.
  • Intercalary cells: Small regenerative cells that function as epithelial stem cells.

• The epithelial lining undergoes cyclical hormonal changes during the menstrual cycle.

• The core of each mucosal fold contains highly vascular connective tissue.

Muscle Layer

• Composed of:
  1. An inner circular smooth muscle layer.
  2. An outer longitudinal smooth muscle layer.

• The circular layer is particularly prominent in the isthmus and assists in regulating transport of the oocyte or embryo toward the uterus.

Serosa/Peritoneal Coat

The outer surface is covered by a thin connective tissue layer and mesothelium (visceral peritoneum).

Functions of Fallopian Tube

1. Facilitates bidirectional transport, moving sperm toward the ampulla and transporting the oocyte or embryo toward the uterus.
2. Serves as the primary site of fertilization.
3. Provides nutritive secretions that support gametes and the early developing embryo.
4. Unlike most regions of the gastrointestinal tract, the uterine tube lacks both muscularis mucosae and submucosa.

Uterus

• The uterus is a hollow, muscular reproductive organ located in the pelvic cavity.
• It is typically pear-shaped and is divided into three main regions:

• Fundus: The dome-shaped superior portion located above the openings of the uterine tubes.
• Body: The central and largest part of the uterus.
• Cervix: The lower cylindrical portion that projects into the vagina and is connected to the body by the isthmus.
• The cervical canal communicates with:
  • The uterine cavity through the internal os.
  • The vagina through the external os.

Histology of Uterus

The uterine wall consists of three layers:

1. Endometrium

• The endometrium is the mucosal lining of the uterus.
• It is composed of:
  • Simple columnar epithelium.
  • Simple tubular uterine glands lined by columnar cells.
  • A highly vascular endometrial stroma containing connective tissue, blood vessels, and glands.
• This layer undergoes cyclical changes during the menstrual cycle.

2. Myometrium

• The myometrium is the thickest layer of the uterine wall and is composed of smooth muscle.
• Smooth muscle fibers are arranged in:
  • An inner longitudinal layer.
  • A middle interlacing layer rich in blood vessels, known as the stratum vasculare.
  • An outer longitudinal layer.
• During pregnancy, myometrial cells undergo both hypertrophy and hyperplasia to accommodate fetal growth.
• Contraction of the myometrium, stimulated by oxytocin, plays a key role in labor and childbirth.

3. Perimetrium

• The outer covering of the uterus is the perimetrium, which forms part of the visceral peritoneum.
• It consists of:
  • An outer mesothelial layer (simple squamous epithelium).
  • An inner layer of vascular connective tissue.

Strata of Endometrium

• The endometrium is organized into three layers:

• Stratum compactum: The superficial, densely cellular layer containing the upper portions of uterine glands.
• Stratum spongiosum: The intermediate layer composed of loose connective tissue and dilated glandular segments.
• Stratum basale: The deepest layer adjacent to the myometrium, containing regenerative cells responsible for renewal of the endometrium after menstruation.

Histological Changes in Endometrium

• The endometrium undergoes cyclical structural changes during the menstrual cycle under the influence of ovarian hormones.

Proliferative Phase

• This phase is primarily regulated by estrogen and involves regeneration of the endometrium from the stratum basale following menstruation.
• Surface epithelium and uterine glands proliferate rapidly.
• Uterine glands appear straight, narrow, and tubular.
• Endometrial stroma increases in volume, causing the endometrium to thicken to approximately 3–4 mm.
• Spiral arteries elongate and extend into the developing functional layer.

Menstrual Phase

• This phase is predominantly controlled by progesterone released from the corpus luteum.
• Uterine glands become highly coiled and tortuous, producing a characteristic saw-toothed appearance.
• Glandular cells accumulate glycogen and secrete nutrient-rich fluid to support potential implantation.
• Spiral arteries become more convoluted and vascularity increases.
• Stromal edema develops due to fluid accumulation.
• Stromal cells enlarge and accumulate glycogen and lipids, producing the decidual reaction.

Menstrual Phase

• Withdrawal of estrogen and progesterone due to corpus luteum regression causes constriction of spiral arteries.
• Reduced blood flow leads to ischemia, tissue breakdown, and shedding of the functional layer of the endometrium.
• Prostaglandins and proteolytic enzymes contribute to menstrual bleeding.
• The stratum basale remains intact because it receives blood from straight arteries and serves as the source for endometrial regeneration in the next cycle.

Table 20.1: Differences between endometrium of proliferative and secretory phases

Feature	Proliferative (Follicular/Preovulatory) Phase	Secretory (Luteal/Postovulatory) Phase
Dominant hormone	Estrogen	Progesterone
Endometrial thickness	Approximately 3–4 mm	Approximately 6–7 mm
Endometrial layers	Initially, the endometrium is mainly represented by the stratum basalis, with regeneration of the functional layer occurring during this phase	All layers of the endometrium, including the functional layer, are fully developed
Uterine glands	Long, relatively straight glands with narrow lumina and wide spacing between adjacent glands	Highly coiled, corkscrew-shaped glands that are closely packed and possess wider lumina
Glandular secretions	Minimal secretory activity	Abundant secretory activity; glandular lumina may contain accumulated secretions
Decidual change	Absent	Present, particularly in the stromal cells
Intracellular glycogen	Absent or minimal	Markedly increased due to progesterone stimulation
Spiral arteries	Slightly tortuous	Highly coiled and elongated
Stromal appearance	Dense cellular stroma with active cell proliferation	Edematous stroma with prominent predecidual changes
Primary purpose	Regeneration and growth of the endometrium following menstruation	Preparation of the endometrium for implantation of a fertilized ovum

Cervix Of Uterus

• The cervix is the lower cylindrical portion of the uterus and contains a narrow passage known as the cervical canal.
• The cervical canal communicates with the uterine cavity through the internal os and opens into the vagina through the external os.
• The portion of the cervix projecting into the vagina is called the portio vaginalis (ectocervix).

Histology of Cervix

• Cervix shows endocervix (mucous membrane) and muscle layer.

Endocervix

• The cervical canal is lined by simple columnar mucus-secreting epithelium.
• This epithelium rests on a loose connective tissue lamina propria.
• The lamina propria contains branched tubular cervical glands that secrete mucus rich in antimicrobial substances, including lysozyme.

Cervical Stroma

• Beneath the mucosa lies a thick layer of fibroelastic connective tissue containing a relatively small amount of smooth muscle.
• The abundant elastic fibers allow cervical expansion and dilation during childbirth.

Ectocervix (Portio Vaginalis)

• The ectocervix is lined by nonkeratinized stratified squamous epithelium, continuous with the vaginal epithelium.
• The junction between the columnar epithelium of the endocervix and the squamous epithelium of the ectocervix forms the transformation zone, an important site for cervical pathology.

Vagina

• The vagina is a fibromuscular, elastic canal that extends from the cervix to the external genital region.
• It is approximately 8–10 cm long and serves as the female copulatory organ and birth canal.

Histology of Vagina

• Vagina has three layers: Mucosa, muscle layer, and adventitia.

Mucosa

• The mucosa forms numerous transverse folds (rugae) that allow distension.
• It is lined by nonkeratinized stratified squamous epithelium, which may show slight keratinization in certain conditions.
• During the follicular phase, epithelial cells accumulate glycogen under estrogenic influence.
• Glycogen content decreases during the secretory phase.
• The lamina propria is broad, highly vascular, and rich in elastic connective tissue.
• The vaginal mucosa lacks glands; lubrication is mainly derived from cervical mucus and transudation from blood vessels.

Muscular Layer

• The muscular coat consists of smooth muscle arranged in:
  • An inner circular layer.
  • An outer longitudinal layer.

• Numerous elastic fibers contribute to vaginal elasticity.
• The lower end of the vagina is supported by fibers of the bulbospongiosus muscle and other pelvic floor muscles.

Adventitia

• The outermost layer is adventitia, composed of connective tissue containing blood vessels, lymphatics, nerves, and elastic fibers, which anchor the vagina to surrounding structures.

Click to see: Medical Disclaimer and Copyright Notice