Lecture 4: Female tract, oogenesis and endocrine control (II)

Question 1

Describe the size and growth of the Uterus

Answer 1

• The uterus is about 7.5 cm long and pear shaped.
• The non-pregnant uterus has a luminal volume of about 10mls
• The pregnant uterus contains about 5 litres of baby, amniotic fluid
and placenta
• i.e. major changes in the physiology of the uterus are required during
pregnancy

The initial growth of the uterus is at least partially under the control of oestrogen (+ progesterone) as ectopic implantation leads to some of the initial growth

However, growth is largely due to stretching of existing cells rather than proliteration of cells.

Question 2

Describe the position of the uterus

Answer 2

• The uterus is normally
anteverted, ie the top of the
uterus faces forwards

• This means the fetus has to turn
90o to be born via the vagina

• Retroverted uterus occurs in 20-
25% of women and is “normal”

Question 3

Name the anatomy of the uterus

Answer 3

• The “top” of the uterus is the fundus
• The bottom of the uterus is continuous with the cervix

• The uterus consists of three main layers

1. The serosa (perimetrium)
2. The muscular myometrium
3. The inner endometrium

Question 4

Describe the Myometrium

Answer 4

The myometrium makes up the bulk of the uterine tissue (about 90%)

The main function of the myometrium is the forceful expulsion of the fetus at parturition

The myometrium is approximately 10mmthick and this d_oes not change significantly_ during the menstrual cycle.

Question 5

What is the decidua?

Answer 5

Where the human embryo implants

2 Definitions

1) Tissue that is lost during menstruation
2) (more accurate) Tissue that dissociates with the uterus when the placenta is delivered.

Question 6

Describe the uterine/endometrial cycle

Answer 6

• The endometrium becomes decidualized after each menstural cycle
• Cycle
  
  • Menses
  • Proliferative phase (uterus is regenerating following menstruation)
  • Secretory phase (phase associated with potential pregnancy where the glands in the endometrium are producing substances that help implant the embryo)

Question 7

What are the phases of the OVARIAN and UTERINE cycle?

Answer 7

Ovarian:

1) Follicular
2) Luteal

Endometrial

1) Menses
2) Proliferative
3) Secretory

Question 8

Describe the Uterine cycle-menstrual cycle

Answer 8

1) Menses: Menstruation (over 5-6 days) and the tissue of the endometrium of the functional layer becomes necrotic and is shed (~30ml of blood)
2) Proliferation: Menstruation ceases, and the endometrial tissue starts to regenerate itself. At the end of the follicular phase = at the end of the proliferative phase, increases in concentration of estrogen. Estrogen goes into the uterus and help stimulate cell growth
3) Secretory phase: The glands start to secrete products to support pregnancy. In the luteal phase, progesterone is predominantly being secreted. Progesterone comes from the corpus luteum which is also producing estrogen. The Progesterone is acting on the glandular cells in the uterus and cause them to release secretions into the glands.

Question 9

What does the estrogen and progesterone do on the uterus?

Answer 9

2) Proliferation: Menstruation ceases, and the endometrial tissue starts to regenerate itself. At the end of the follicular phase = at the end of the proliferative phase, increases in concentration of estrogen. Estrogen goes into the uterus and help stimulate cell growth
3) Secretory phase

: The glands start to secrete products to support pregnancy. In the luteal phase, progesterone is predominantly being secreted. Progesterone comes from the corpus luteum which is also producing estrogen. The Progesterone is acting on the glandular cells in the uterus and cause them to release secretions into the glands.

Question 10

What is the decidual reaction?

Answer 10

• • In preparation for implantation the endometrium undergoes changes called the decidual reaction
    
    • The stroma of the endometrium becomes oedematous, stromal fibroblasts expand and fill with glycogen –an energy source for the embryo
    • Decidual reaction occurs only in a few species –occurs spontaneously each menstrual cycle in women but only after implantation in other species.

Question 11

In preparation for implantation the endometrium undergoes changes called the ____________

Answer 11

• In preparation for implantation the endometrium undergoes changes called the decidual reaction
  
  • The stroma of the endometrium becomes oedematous, stromal fibroblasts expand and fill with glycogen –an energy source for the embryo
  • Decidual reaction occurs only in a few species –occurs spontaneously each menstrual cycle in women but only after implantation in other species.

Question 12

In women, the embryo implants ________-

Answer 12

In women, the embryo implants _entirely inside the wall of the uterus (_not in the uterine lumen)

this is not the case with many other animals

Question 13

What are the layers of the Endometrium?

Answer 13

Question 14

In mouse and rats but NOT HUMANS, decidualisation occurs…..

Answer 14

post implanation (not before)

Question 15

What is decidualization?

Answer 15

Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy.

Question 16

Describe the Uterine blood supply

Answer 16

• Uterine Artery feeds into Arcuate arteries which feeds into spiral arteries and straight arteries.
• The key vessels that supply blood to the endometrium and, during pregnancy, the placenta are the spiral arteries
  • These terminal vessels are tonically active like other arteries.
  • During menses the s_piral artery terminal segments_ are lost along with the other rest of the functionalis layer of the endometrium
  • To prevent exsanguination (severe loss of blood) the spiral arteries undergo spasm.
  • In the proliferative phase of the cycle the spiral arteries (and endometrial glands) grow very rapidly
    
    • Since they grow faster than the surrounding stromal the arteries develop into spring-like coils.

Question 17

Describe the endometrial change across the menstrual cycle

Answer 17

• Under the influence of estrogen (primarily), you get a massive proliferation of the stoma of the endometrial tissue.
• You also get the growth of the spiral arteries, (which are supposidly growing faster than the stroma)
• And also growth of the glands
• Progesterone is being released in the luteal phase, and is making the glands secrete. The fibroblasts are filling up with glycogen, giving implanted embryos stuff to eat.

Question 18

How long is a menstrual cycle?

Answer 18

4 weeks ~28 days

But tends to shorten as women age. (30 for young women, 25 for older women)

And each cycle can vary in length

Luteal phase = 12.7 days

Follicular phase = 17.6 days

Question 19

Describe the different things you look at when Dating the Endometrium

Answer 19

• Gland mitoses
  
  • Indicates proliferation.
  • They occur during menstruation because repair and breakdown are progressing simulatneously at that time
• Pseudostratification of Nuclei
  
  • Characteristic of the proliferation phase but persists until active secretion begins
  • It is not resumed until the glands have involuted during menstruation
• Basal vacuolation
  
  • Earliest morphological evidence of ovulation found int he endometrium
  • Begins approx 36-48 hours following ovulation
• Secretion
  
  • This curve represents visible secretion in the gland lumen; active secretion falls off more abruptly
  • In the later stages the seceretion becomes inspissated
• Stromal edema
  
  • This factor varies with the individual, particuarly the rise during proliferation which may be almost absent.
  • The edema which accompanies secretion is more constant
• Pseudodecidual reaction
  
  • Evident first around the arterioles and progresses until just before menstruation
  • A superficial compact layer is formed
• Stromal mitosis
  
  • These are most abdunent during the proliferative phase, absent during active secretion but reappear during the stage of precidual formation
• Leucocytic infiltration
  
  • Throughout the cycle, there are always a few lymphocytes.
  • Polymomrphonuclear infiltration begins about 2 days before the onset of flow.

Question 20

Date this endometrial tissue

Answer 20

Mid proliferative stage

1) White-unstained areas in the stromal tissue because of estrogen. The vessles become leaky in the presence of estrogen.
2) Show lots of glands. (left) , there are also Mitotic bodies (right). These are chromosomes that have lined up. This tells us that this is a rapidly proliferative tissue.

Question 21

Date this endometrial tissue

Answer 21

Early luteal

1) Very trotuous glands (not straight)
2) Basal vaculotation
3) Glandular secretions (from the glands- epithelial cells)

Question 22

What feature of the endometrial tissue is this?

Answer 22

Leucocyte infiltration

(polymorphs)

Question 23

What does the estrogen and progesterone stimulate and what does the progesterone inhibit in the uterus?

Answer 23

• Estrogen stimulates:

1. epithelial and stromal cell proliferation
2. stromal oedema (2 peaks of estrogen, so 2 different levels of stromal oedma)
3. _glandular secretion_s (serous)
4. synthesis of i_ntracellular progesterone receptors_
   (estrogen priming)
5. myometrial activity

• Progesterone stimulates:

1. glandular secretions (thick) in luteal phase
   (against an oestrogenbackground)
2. stromal cell proliferation

• Progesterone inhibits:
  1. myometrial activity

Question 24

What is ectopic implantation?

Answer 24

Ectopic implantation can occur anywhere in the abdominal cavity.

Ectopic implantation is most common inside the fallopian tubes

Question 25

Many textbooks indicate that the decidual reaction and decidua is required for implantation

This is not true- how do we know?

Answer 25

Ectopic pregnancies

Question 26

What is endometriosis?

Answer 26

• Ectopic endometrium
• 6-10% of women
• Causes chronic pelvic pain
• Association with infertility
• Essentially e_ndometrial tissue outside of the uterus_ often on the ovaries

•Causes –not really known

• Retrograde menstruation
• Transport of endometrial cells via blood or lymphatics
• Growth of endometrial-like tissue from stem cells

Question 27

What area is the target for HPV?

Answer 27

Cervical junctional zones

Question 28

Describe the cervical cancer

Answer 28

• Cervical cancer is caused by HPV infection and a vaccine exists for serotypes 16 and 18 –other serotypes also cause Ca-cervix.
• Regular cervical smear tests every three years are recommended for women, if they have ever been sexually active, from the age of 20 until they turn 70.
• Having regular cervical smears can reduce a woman’s risk of developing cervical cancer by 90 percent!