|  | Home
| School of Anatomy and Human Biology - The University of Western Australia
| Blue Histology - Female Reproductive System

Topics | Lab Guides and Images
Female Reproductive System |
The Ovaries Ovarian Follicles Atresia Corpus luteum | Ovary - Primordial and Primary Follicles - H&E
Ovary - Corpus luteum - H&E
Oviduct | Oviduct - H&E
Uterus | Uterus - Endometrium - H&E
Vagina | Vagina - H&E
Mammary Glands | Lactiferous Duct and Mammary Gland - H&E

#### Additional Resources

These links will open a new browser window.

Large Images
  Search the Large Images page with these keywords: female reproductive system, ovary, oviduct, uterus, labium minorum, placenta, mammary gland, primordial follicle, primary follicle, secondary follicle, corpus luteum, corpus albicans, cumulus oophorus, germinal epithelium, myometrium, endometrium, uterine gland, chorionic villi, cytotrophoblast, syncytiotrophoblast, theca lutein cell, granulosa lutein cell, or peg cell.
VScope
  Magnification & Stage Simulation: ovary, monkey, H&E
Self Assessment
  Choose subject area "reproductive and urinary system" on the Quiz page. This subject area covers the male reproductive system and the urinary system in addition to the female reproductive system.

### Female Reproductive System

This section focusses on the internal female reproductive organs: the ovaries, oviducts, uterus and vagina. We will also have a look at the mammary gland, an accessory reproductive gland. The external female genitalia include the labia minora and majora, clitoris and vestibule.

#### The Ovaries

The ovaries have two functions - "production" and ovulation of oocytes and the production and secretion of hormones. The ovary is attached to the broad ligament by a short fold of peritoneum, called the mesovarium (or ligament of the ovary), through which vessels and nerves pass to the ovary and enter it at the hilus of the ovary.

The surface of the ovary is covered by a single layer of cuboidal epithelium, also called germinal epithelium. It is continuous with the peritoneal mesothelium. Fibrous connective tissue forms a thin capsule, the tunica albuginea, immediately beneath the epithelium.

Like so many other organs the ovary is divided into an outer cortex and an inner medulla. The cortex consists of a very cellular connective tissue stroma in which the ovarian follicles are embedded. The medulla is composed of loose connective tissue, which contains blood vessels and nerves.

#### Ovarian Follicles

Ovarian follicles consist of one oocyte and surrounding follicular cells. Follicular development can be divided into a number of stages.

Development represents a morphological continuum, and it may not be possible to assign all follicles to a specific stage. This said, it's pretty easy most of the time.

Primordial follicles

  are located in the cortex just beneath tunica albuginea. One layer of flattened follicular cells surround the oocyte (about 30 µm in diameter). The nucleus of the oocyte is positioned eccentric in the cell. It appears very light and contains a prominent nucleolus.
  Most organelles of the oocyte aggregate in the centre of the cell, where they form the vitelline body (probably not visible in any of the available preparations).

The primary follicle

  is the first morphological stage that marks the onset of follicular maturation (Which hormone stimulates follicular maturation and where is this hormone produced?). The previously flattened cell surrounding the oocyte now form a cuboidal or columnar epithelium surrounding the oocyte. Their cytoplasm may have a granular appearance, and they are for this reason also called granulosa cells. The continued proliferation of these cells will result in the formation of a stratified epithelium (with a distinct basement membrane) surrounding the oocyte. The zona pellucida (glycoproteins between interdigitating processes of oocyte and granulosa cells) becomes visible. Parenchymal cells of the ovary surrounding the growing follicle become organised in concentric sheaths, the theca folliculi.

Secondary follicle

  Small fluid-filled spaces become visible between the granulosa cells as the follicle reaches a diameter of about 400 µm. These spaces enlarge and fuse to form the follicular antrum, which is the defining feature of the secondary follicle. The oocyte is now located eccentric in the follicle in the cumulus oophorus, where it is surrounded by granulosa cells. The theca folliculi differentiates with the continued growth of the follicle into a theca interna and a theca externa. Vascularization of the theca interna improves, and the spindle-shaped or polyhedral cells in this layer start to produce oestrogens. The theca externa retains the characteristics of a highly cellular connective tissue with smooth muscle cells. The oocyte of the secondary follicle reaches a diameter of about 125 µm. The follicle itself reaches a diameter of about 10-15 mm.

The mature or tertiary or preovulatory or Graafian follicle

  increases further in size (in particular in the last 12h before ovulation). The Graafian follicle forms a small "bump" on the surface of the ovary, the stigma (or macula pellucida). The stigma is characterised by a thinning of the capsule and a progressive restriction of the blood flow to it. Prior to ovulation the cumulus oophorus separates from the follicular wall. The oocyte is now floating freely in the follicular antrum. It is still surrounded by granulosa cells which form the corona radiata. The follicle finally ruptures at the stigma and the oocyte is released from the ovary.

Ovary, macaque - H&E
Identify cortex and medulla at low magnification and verify the presence of large numbers of blood vessels in the medulla. Now have a look at the cortex at medium/high magnification. Identify the cuboidal epithelium covering the ovary and the underlying tunica albuginea. Find a part of the cortex where you can observe primordial, primary and secondary follicles.
Draw this section of the cortex with its follicles, the surrounding theca (if present), connective tissue stroma, tunica albuginea and epithelium.

#### Atresia

Atresia is the name for the degenerative process by which oocytes (and follicles) perish without having been expelled by ovulation. Only about 400 oocytes ovulate - about 99.9 % of the oocytes that where present at the time of puberty undergo atresia. Atresia may effect oocytes at all stages of their "life" - both prenatally and postnatally. By the sixth month of gestation about 7 million oocytes and oogonia are present in the ovaries. By the time of birth this number is reduced to about 2 million. Of these only about 400.000 survive until puberty.

Atresia is also the mode of destruction of follicles whose maturation is initiated during the cyclus (10-15) but which do not ovulate. Atresia is operating before puberty to remove follicles which begin to mature during this period (none of which are ovulated). Given that atresia affects follicles at various stages of their development it is obvious that the process may take on quite a variety of histological appearances.

#### The Corpus luteum

The corpus luteum is formed by both granulosa cells and thecal cells after ovulation has occurred. The wall of the follicle collapses into a folded structure, which is characteristic for the corpus luteum. Vascularization increases and a connective tissue network is formed. Theca interna cells and granulosa cells triple in size and start accumulating lutein (Which hormone stimulates this process? Where is this hormone produced?) within a few hours after ovulation. They are now called granulosa lutein cells and theca lutein cells and produce progesterone and oestrogens.

Hormone secretion in the corpus luteum ceases within 14 days after ovulation if the oocyte is not fertilised. In this case, the corpus luteum degenerates into a corpus albicans - whitish scar tissue within the ovaries.

Hormone secretion continues for 2-3 month after ovulation if fertilisation occurs.

Corpus luteum - H&E
Hold the slide against the light and try to identify the corpus luteum. It appears as a large (5mm-1cm) rounded but somewhat irregularly shaped structure in the periphery of the ovary. It stains homogeneously bright red except from a reddish irregular structure at its core. Now have a look using the low magnification and verify the "folded" appearance of the tissue forming the corpus luteum. You may be able to find spots in the periphery of the corpus luteum in which a fairly thin layer of slightly darker cells surround the otherwise light red cell forming most of the corpus luteum. The dark cell represent theca lutein cell the lighter ones are granulosa lutein cells.
Sketch the corpus luteum and ovary at low magnification and make sure that the relative size of the corpus luteum becomes apparent in your sketch. Draw, if possible, a spot where you can differentiate between theca and granulosa lutein cells.

#### The Oviduct

The oviduct functions as a conduit for the oocyte, from the ovaries to the uterus. Histologically, the oviduct consists of a mucosa and a muscularis. The peritoneal surface of the oviduct is lined by a serosa and subjacent connective tissue.

The mucosa

  is formed by a ciliated and secretory epithelium resting on a very cellular lamina propria. The number of ciliated cells and secretory cells varies along the oviduct (see below). Secretory activity varies during the menstrual cycle, and resting secretory cells are also referred to as peg-cells. Some of the secreted substances are thought to nourish the oocyte and the very early embryo.

The muscularis

  consists of an inner circular muscle layer and an outer longitudinal layer. An inner longitudinal layer is present in the isthmus and the intramural part (see below) of the oviduct. Peristaltic muscle action seems to be more important for the transport of sperm and oocyte than the action of the cilia.

Texts usually refer to four subdivisions of the oviduct.

1. The infundibulum is the funnel-shaped (up to 10 mm in diameter) end of the oviduct. Finger-like extensions of its margins, the fimbriae, are closely applied to the ovary. Ciliated cells are frequent. Their cilia beat in the direction of
2. the ampulla of the oviduct. Mucosal folds, or plicae, and secondary folds which arise from the plicae divide the lumen of the ampulla into a very complex shape. Fertilization usually takes place in the ampulla.
3. The isthmus is the narrowest portion (2-3 mm in diameter) of the parts of the oviduct located in the peritoneal cavity. Mucosal folds are less complex and the muscularis is thick. An inner, longitudinal layer of muscle is present in the isthmus and the
4. last, intramural part of the oviduct, which penetrates the wall of the uterus. The term "intramural" should be familiar to you ..... The mucosa is smooth, and the inner diameter of the duct is very small.

Oviduct is a nice descriptive term, but (sigh) not the only one commonly used for these structures - you will also find the terms Fallopian tubes or uterine tubes. The term salpinx (Greek, trumpet) seems to have passed its "use-by-date" in many histology text but (sigh) not in pathology, where salpingitis refers to chronic or acute inflammation of the oviduct. Let's see how "tubal inflammation" will fare in the future.

Obstruction of the oviduct as a consequence of salpingitis is one possible cause of infertility, and alterations of luminal structure by inflammatory processes are a risk factor for tubal pregnancies.

Oviduct - H&E and Ovary, macaque - H&E
Unfortunately, we do not have many oviduct slides, but some sections of the macaque ovary and the uterus slide contains segments of the oviduct. In the former you should be able to see both the muscularis and the folded mucosa. Ciliated cells and peg-cells are present. In the intramural part of the oviduct (uterus slide) the mucosa is smooth and ciliated cells are rare or absent. The intramural part of the uterus should remind you of a structure in the male reproductive system - Which one?
Draw part of the wall of the oviduct, identify the segment and, if possible, ciliated and peg cells.

#### The Uterus

The uterus is divided into body (upper two-thirds) and cervix. The walls of the uterus are composed of a mucosal layer, the endometrium, and a fibromuscular layer, the myometrium. The peritoneal surface of the uterus is covered by a serosa.

Myometrium

  The muscle fibres of the uterus form layers with preferred orientations of fibres (actually 4), but this is very difficult to see in most preparations. The muscular tissue hypertrophies during pregnancy, and GAP-junctions between cells become more frequent.

Endometrium

  The endometrium consists of a simple columnar epithelium (ciliated cells and secretory cells) and an underlying thick connective tissue stroma. The mucosa is invaginated to form many simple tubular uterine glands. The glands extend through the entire thickness of the stroma. The stromal cells of the endometrium are embedded in a network of reticular fibres. The endometrium is subject to cyclic changes that result in menstruation. Only the mucosa of the body of the uterus takes part in the menstrual cycle.

The endometrium can be divided into two zones based on their involvement in the changes during the menstrual cycle: the basalis and the functionalis.

- The basalis is not sloughed off during menstruation but functions as a regenerative zone for the functionalis after its rejection.
- The functionalis is the luminal part of the endometrium. It is sloughed off during every menstruation and it is the site of cyclic changes in the endometrium. These cyclic changes are divided into a number of phases: proliferative (or follicular), secretory (or luteal), and menstrual.

Uterus, proliferative phase - H&E
Identify the muscular wall of the uterus and the endometrium lining the lumen of the uterus. Identify uterine glands embedded in the stroma of the endometrium. Finally try to find a spiral artery. These are arteries ascend through the endometrium and form a coil/spring like structure while they do so. How would you expect this structure to look like in a section?
Sketch a small section of the endometrium.

#### Vagina

The vagina is a fibromuscular tube with a wall consisting of three layers: the mucosa, muscularis and adventitia of the vagina

Mucosa

  The stratified squamous epithelium (deep stratum basalis, intermediate stratum spinosum, superficial layers of flat eosinophilic cells which do contain keratin but which do not normally form a true horny layer) rests on a very cellular lamina propria (many leukocytes). Towards the muscularis some vascular cavernous spaces may be seen (typical erectile tissue).

Muscularis

  Inner circular and outer longitudinal layers of smooth muscle are present. Inferiorly, the striated, voluntary bulbospongiosus muscle forms a sphincter around the vagina.

Adventitia

  The part of the adventitia bordering the muscularis is fairly dense and contains many elastic fibres. Loose connective tissue with a prominent venous plexus forms the outer part of the adventitia.

| Vagina, human - H&E Identify the layers of the vagina. Note that the organization of the wall of the vagina corresponds in many respects to the organization of the wall of the oesophagus. It should not be necessary to do a drawing. Compare your observations in the vagina with those in the oesophagus. Try to define how the layers differ although they are composed of similar tissue types.

#### Female Accessory Reproductive Glands - Mammary Glands

The mammary glands are modified glands of the skin. Their development resembles that of sweat glands. They are compound branched alveolar glands, which consist of 15-25 lobes separated by dense interlobar connective tissue and fat. Each lobe contains an individual gland. The excretory duct of each lobe, also called lactiferous duct, has its own opening on the nipple.

The lactiferous duct has a two layered epithelium - basal cells are cuboidal whereas the superficial cells are columnar. Beneath the nipple, the dilated lactiferous duct forms a lactiferous sinus , which functions as a reservoir for the milk. Branches of the lactiferous duct are lined with a simple cuboidal epithelium. The secretory units are alveoli, which are lined by a cuboidal or columnar epithelium. A layer of myoepithelial cells is always present between the epithelium and the basement membrane of the branches of the lactiferous duct and the alveoli.

The above description corresponds basically to the appearance of the resting mammary gland. Pregnancy induces a considerable growth of the epithelial parenchyma leading to the formation of new terminal branches of ducts and of alveoli in the first half of pregnancy. Growth is initiated by the elevated levels of oestrogen and progesterone produced in the ovaries and placenta. Concurrently, a reduction in the amount of intra- and interlobular connective tissue takes place. The continued growth of the mammary glands during the second half of pregnancy is due to increases in the height of epithelial cells and an expansion of the lumen of the alveoli. They contain a protein-rich (large amounts of immunoglobulins) eosinophilic secretion - the colostrum or foremilk).

Secretion of milk proteins proceeds by exocytosis (merocrine secretion), whereas lipids are secreted by apocrine secretion. Secretion is stimulated by prolactin. Prolactin secretion in turn is stimulated by sensory stimulation of the nipple, which also initiates the so-called milk ejection reflex via the secretion of oxytocin from the neurohypophysis. Milk is ejected from the glandular tissue into the lactiferous sinuses - now it's up to the baby to get things out.

The glandular tissue of the mammary gland is frequently subject to pathological changes - the most serious being mammary cancer, which is the most frequent malignancy in women (about 6.5% of all women develop the disease).

Non-lactating breast - H&E and Lactating breast, human - H&E
Identify lactiferous ducts in the section of the non-lactating breast. See if you can identify resting alveoli and lactiferous sinuses.
Draw a nice lactiferous duct and, if possible, a few resting alveoli.
Identify the secretory alveoli and interlobular ducts in the slide of the lactating mammary gland. Do all parts of the secretory tissue look similar? Why/why not?
Draw and label part of the secretory tissue.

page content and construction: Lutz Slomianka
last updated: 9/01/04