Female reproductive system

Oviduct and Uterus

GV Childs, Ph.D.
Assigned reading: pp472-478; pp 482-483

Test your knowledge of the oviduct (fallopian tubes) and uterus

1. Describe the wall of the oviduct
2. Describe each region of the oviduct and its function
3. How is the mucosa structured to assist fertilization and transport?
4. What is the function of the ciliated cells and the direction of movement?
   What happens to cilia if the estrogen levels are not maintained?
5. What are Peg cells? 
6. How does the oviduct work?
7. What are the anatomical regions of the uterus?
8. Describe the wall of the uterus.
9. What is the adventitia and where is it a serosa?
10. What is the myometrium and how is it regulated, hormonally?
11. What is the endometrium?
12. Define the regions of the endometrium and their functional significance.
13. Describe the vascular supply to the endometrium.
14. Define the time and events during the menstrual phase of the menstrual cycle.
15. Define the events during the proliferative phase of the menstrual cycle.
16. Define the events during the secretory phase of the menstrual cycle.
17. Review the hormonal changes during the cycle that lead to changes in the ovary and the uterus
18. Describe the structure and function of the cervix.
19. Describe the wall of the vagina.
20. Describe the external genitalia.

Oviduct

Wall: 

Outer layer is serosa (squamous epithelium + connective tissue);
inner circular and outer muscular layers (smooth);
lamina propria connective tissue from mucosa to muscularis.

Regions: 

Infundibulum--fimbriated (fringe) end that scans the ovary and captures the secondary oocyte
Ampulla--expanded region (like a trumpet) where the oocyte is fertilized.
Isthmus--narrow region that connects to the uterus at the interstitial (intramural) region

Mucosa

Structured to nourish and move the oocyte and fertilized embryo to the uterus.
Ciliated cells: Movement is done by ciliated cells (cilia is very sensitive to estrogens; if estrogen level drops, cells will lose cilia). Cilia beat toward uterus which means the spermatozoa must swim upstream, against a current of liquid secreted by Peg Cells.
Peg cells have no cilia.  They secrete a nutritive fluid that facilitates capacitation of spermatozoa. Note: is this required?  What about in vitro fertilization? 

Also, secretion from Peg cells nourishes embryo as it passes down the 12 cm tube.
Peg cells also secrete fluid that inhibits microorganisms that could invade from the peritoneal cavity.

Electron micrograph in text shows great view of two cell types. Below are some LM views.

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Region through the infundibulum or ampulla.  Note the long mucosal folds. Use your knowledge of histology to name the layers.  In the following photographs of the mucosa, can you find Peg cells and ciliated cells?  The underlying connective tissue is the lamina propria.

How does the oviduct work?

 Smooth muscle wall constricts and contracts.  Distends the oviduct to bring it into contact with the ovary.  May be a little like a "vacuum cleaner" driven by fluid movement...the fimbriated end swishes over the surface of the ovary as the beating cilia beats fluid (expelled and secreted) towards the uterus.  This motion helps capture and propel the oocyte.

Uterus

Muscular, pear shaped organ which is connected to the oviduct at the upper body  and to the cervix and vagina in the lower region.  It has three anatomically distinct regions:  Body (oviducts connect, upper); fundus (just above the exit to cervix); Cervix: exit, protrudes into the vagina.

Wall is made of three layers:  Adventitia (or serosa)=connective tissue with epithelium; Myometrium =smooth muscle, running in three ill defined layers: inner longitudinal, middle circular, and outer longitudinal.  Endometrium (mucosa) includes simple columnar epithelium; branched tubular glands and lamina propria.

Adventitia

Retroperitoneal (anterior) portion covered by adventitia (no epithelia).  The fundus and posterior portion covered by serosa (connective tissue + squamous mesothelial cells).

Myometrium

Thick, smooth muscle wall. Inner and outer longitudinal and middle circular (region that is heavily vascularized). Estrogen stimulates proliferation and growth (during pregnancy or midcycle-luteal phase) Low estrogen causes atrophy and apoptosis of some cells (menstrual phase and after pregnancy).

Under influence of oxytocin from posterior pituitary and prostaglandins produced locally.  Some contractions are stimulated by oxytocin which is released during intercourse (after distension of the vagina).  Contractions at midcycle help with movement of embryo. Contractions during menstruation cause cramps. 

Endometrium

Phases of the endometrium: match the follicular and luteal phases of the ovary.

Day 1-4: Menstrual

Also day 1 of follicular phase. First day of bleeding and full proof that corpus luteum from previous cycle is non-functional. Progesterone and estrogen are both lower.
Coiled arteries constrict, reduce supply of oxygen to functionalis.
Glands shut down, leukocytes invade and area becomes necrotic.
Arteries rupture and bleeding includes functionalis and some blood loss.
On day 4-5, the basalis cells begin to proliferate, restore the epithelium for the next cycle. The 2 photos below represent the basalis in the menstrual phase.

Days 4-14: Proliferative

As its name implies, the glands and connective tissue are restored by proliferation from the base.  Tubular glands are at first straight.  They begin to accumulate glycogen which is seen as droplets in the cellular cytoplasm. The functionalis has been fully restored by day 14.  This may end the follicular phase in a 28 day cycle.  However, in longer cycles, the proliferative phase is the one that is prolonged.  Thus, a 35 day cycle has a 20-21 day proliforative phase.

Proliferative phase: Note the straight glands and the light stroma. Mitotic figures are frequently seen.  Also, the droplets of glycogen can be seen in some cells

Secretory Phase (lasts 14-16 days)

This is the most constant phase, in terms of time. In 28 day cycles, it lasts from days 15 (after ovulation) to day 28. A longer cycle can vary in the Proliferative phase which means that ovulation may be delayed.  However, there is a fairly constant life-time for the corpus luteum in the face of the inhibited gonadotropins.  If the CL is not rescued by placental gonadotropins in about 10 days, it undergoes apoptosis and involutes.  One defect that may occur is a Short Luteal Phase, which is often seen as a premature drop in progesterone and a luteal phase less than 10 days.  This indicates problems with the corpus luteum and a woman will not be able to build the endometrium sufficiently for implantation. The endometrium continues to proliferate: the glands coil and the stroma becomes more dense.  The secretory products coalesce and on day 16 (2 days after ovulation) there is a characteristic accumulation at the base.  This is often diagnostic in endometrial biopsies of ovulation. Coiled arteries become more coiled and grow into the functionalis.  Thus, by the 22nd day, the endometrium is fully developed and ready for implantation.

These figures show the 16 day stage with the basal droplet of glycogen (V).  A more advanced secretory phase is seen in the right photo.  Note the dense stroma, tall cells and coiled appearance of the gland.

During the lecture, we will go over some cases in which endometrial dysfunction is detected by immunolabeling and correlated with infertility.

Lets review the hormonal changes and the events in the ovary and uterus:

Cervix

Region connecting uterus with vagina, actually projects into vagina.  Produces mucous and serous secretions, which are protective and lubricating. Secretions become less viscous (more serous secretions) and thinner at midcycle, under the influence of progesterone. Thicker mucous protects against bacterial infection and may prevent entry of sperm at other times during the cycle (and during pregnancy).  The thinning mucous at midcycle allows entry of sperm.

Cervix has simple colmunar epithelium that grades to stratified squamous, non-keratinized epithelium in the vagina.  The mucosa contains branched cervical glands which secrete the above mentioned products. Photos illustrate the epithelium  and the glands in the lamina propria.  Photos show epithelium (left) and glands (right).

Vagina

Connected to the uterus and the external vestibule (external genitalia).  Wall contains a mucosa, muscularis, and adventitia.

Mucosa is thick, stratified squamous, non-keratinized epithelium.  The epithelium is pale because of the storage of glycogen. There is no muscularis mucosa, so you can use the pale staining epithelium and absence of muscularis mucosa to differentiate the vagina from the esophagus.

Lamina propria connective tissue is well vascularized and contains numerous lymphocytes and neutrophils that reach the lumen by passing through the epithelium spaces. There are no glands, however the extracellular fluid in the lamina propria does add to secretions from cervical glands to help lubricate the vagina during intercourse.

Muscularis is smooth, intermingling.  Skeletal muscle fibers form a sphincter muscle which encircles the vagina at its external opening. 

Outside the muscularis is the adventitia...loose connective tissue.

The following photos show view of the vagina and cervical glands (left) and the vaginal epithelium (right). Note the lighter staining surface vaginal epithelial cells.  They are filled with glycogen which has washed out during histological processing. Breakdown of glycogen produces lactic acid which reduces the pH in the vagina to 3.  This is protective against bacterial infection and limits the life of the sperm in the vagina (prostatic secretions to semen help neutralize pH, however)                                        

External Genitalia (vulva):

These are studied in Gross anatomy and include the labia majora and minora separated by a cleft called the vestibule. In this region are the Glands of Bartholin which secrete mucus and minor vestibular glands which lubricate the area. In virgins, the vagina orifice is partially covered by a fold of epithelia covered connective tissue called the hymen.

The clitoris is located between the folds of the labia minora and is composed of two erectile bodies containing numerous blood vessels and sensory nerves.  The endings include Pacinian and Meissner's corpuscles.  As in the penis, these are sensitized during sexual arousal.

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