Female Reproduction

Front 1

In general terms, what are the goals of the follicular phase and the luteal phase? When do these phases happen (in relation to each other)?

Back 1

Follicular: Recruit and prepare oocyte-containing follicles for ovulation. This phase starts on the first day of the menstrual cycle.

Luteal: prepare support for the fertilized ovum. Occurs ~15 days after follicular phase.

Front 2

List the events of the follicular phase and their signals

Back 2

1.) “Cyclic” recruitment of a pool of antral follicles (oocytes). Signaled by FSH.
2.) Follicle selection of the “dominant” follicle (unknown mechanism for this).
3.) Growth of dominant follicle. Signaled by FSH & LH.
4.) Ovulation

Front 3

Describe the process of oogenesis. What is the key difference between male and female gametogenesis?

Back 3

1.) Primordial germ cells migrate to gonads (in utero).
2.) Mitotic activity of oogonia occurs up to 7th month gestation
3.) Meiosis of oocytes occurs, but is arrested at the diplotene stage until adulthood.

Mitosis occurs during fetal life in females (and ONLY then → finite pool). Mitosis starts in puberty in males and continues throughout life. Also, Meiosis I and II occurs in succession in males. In females it stops in fetal life and recommences in adulthood.

Front 4

When do females stop producing gametes? Meiosis is arrested at what phase in oocytes?

Back 4

Mitosis ends at the 7th month of fetal life → you have your whole life supply by this point.

Meiosis is arrested during Diplotene (prophase)

Front 5

How many follicles are recruited in the cyclic recruitment stage of the follicular phase? What is their fate?

Back 5

4-6 are recruited. Only one will be selected (the “dominant follicle”). The others will become atretic (degenerates and is resorbed before reaching maturity).

Front 6

What is inhibin B? Where is it secreted? When is it secreted?

Back 6

It is secreted by the recruited follicles at the beginning of the cyclic recruitment stage of the follicular phase. It has a slow negative feedback on the pituitary gland to decrease FSH secretion. (Basically signals to the HPA-axis that follicular recruitment was successful.)

Front 7

What are the outer layers of the maturing follicle called? What is the name for the layer inside this outer layer? What is one distinguishing aspect between the two layers? What hormone(s) act on these layers and what do they do?

Back 7

Theca → 2 layers, external is connective tissue capsule, Internal is where the action lies. Theca interna IS vascularized – Both LH and FSH act here. FSH activates the appearance of LH receptors in the Theca internal layer. LH is then able to initiate androgen synthesis in the follicle.

Inside the theca is the Granulosa layer – IS NOT vascularized – FSH ONLY acts here.

Front 8

Where are female androgens synthesized?

Back 8

Within the Theca interna. (They are converted to estradiol in the granulosa layer.)

Front 9

What happens within the granulosa cells?

Back 9

Estrogen precursors synthesized in the theca interna (tesosterone) gets converted into Estradiol. Aromatase is the enzyme that transforms testosterone into estradiol upon signaling by FSH.

Front 10

How must GnRH/LH be delivered for optimal growth of the dominant follicle?

Back 10

Pulsatile release of GnRH is required. Optimal frequency is 1 pulse/90 minutes in humans.

Front 11

How does the body “shut down” menstruation in response to stress, exercise, low caloric intake, etc?

Back 11

A neural response: it slows down the GnRH pulse frequency.

Front 12

What transforms testosterone to estradiol? Where is it located?

Back 12

Aromatase, located in the granulosa cells (after signaling by FSH)

Note: This is an EXPLOSIVE event. The follicle grows very quickly. Estradiol levels can be measured and used as a proxy for follicle size.

Front 13

Describe the negative feedback loop in female reproduction.

Back 13

Estradiol acts on both the hypothalamus and the pituitary gland to reduce release of GnRH and LH.

Front 14

Where is the effect of the increased estradiol environment the strongest, and what is the effect? What are secondary effects of estradiol?

Back 14

Estradiol acts mainly on the endometrium. It causes glandular proliferation.

Secondary effects: estradiol acts on endocervical glands to increase mucus production, change the environment from acidic to alkaline pH, and broaden the cervical canal.

**In a nutshell: the environment is optimized for sperm penetration and facilitates intercourse.

Front 15

Without running any labs, how can you tell if someone is in the follicular phase?

Back 15

Positive Fern Test: Take a drop of cervical mucus on a slide → it will form a fern shape ONLY when estrogen levels are high (during follicular phase). Also, mucus will be more elastic and stretchable during this time.

Front 16

What is the trigger for ovulation?

Back 16

There is a surge in LH release that occurs in synchrony with the explosion of estradiol (positive estradiol feedback loop).

Front 17

What two conditions must occur in order for estrogen to switch from a negative feedback signal to positive feedback (the SURGE)?

Back 17

1.) Estradiol levels have to reach a certain setpoint, demonstrating to the brain that there is an active, dominant follicle there that is secreting estradiol.

2.) Estradiol levels must remain at that setpoint for at least 36 hours (tells the brain that it’s not just a spurt of estrogen → there actually is a structure there).

Front 18

What are the four main effects of the LH surge (i.e. ovulation)?

Back 18

1.) Completion of first meiotic division (creates secondary oocyte)
2.) Change in steroid enzyme activity (aromatase shut down) → shift away from estradiol and towards PROGESTERONE synthesis.
3.) Rupture of follicle and release of oocyte = OVULATION
4.) Capillaries from theca interna invade granulosa layer (which is normally avascular) → follicle transformed into a CORPUS LUTEUM

Front 19

When does ovulation occur in relation to the estrogen surge?

Back 19

The oocyte is released about a day and a half after the estradiol spike.

Front 20

What is the signal for the luteal phase?

Back 20

LH

Front 21

What is the function of the corpus luteum?

Back 21

This functions during the luteal phase. It secretes both estradiol and progesterone. It also secretes INHIBIN A (remember this!)

Front 22

When and where are Inhibin A and Inhibin B secreted?

Back 22

Inhibin A: Secreted by the corpus luteum during the luteal phase.

Inhibin B: Secreted by recruited follicles at the beginning of the follicular phase.

Front 23

What blocks the positive feedback of estradiol?

Back 23

The high progesterone environment blocks the estradiol positive feedback loop. Which makes sense because you don’t want ovulation to occur during the luteal phase of the cycle.

Front 24

What is the impact of the increased progesterone on the uterus?

Back 24

1.) Blocks estradiol positive feedback loop.
2.) Changes endometrial glands in the uterus from “growing” to “secretory” → secretes proteins that are nutrients for the arriving fertilized egg.
3.) Enlarges stromal cells and transforms them into DECIDUAL cells (the “cushy” environment for the egg).
4.) Activates an array of genes active in implantation.

Front 25

What is the impact of the increased progesterone on the cervix?

Back 25

**Basically “undoes” the effects of estradiol … effectively seals the uterine cavity from the outside world.

1.) Decreased mucus production (mucus becomes thick and gooey)
2.) Change from alkaline to acidic pH
3.) Narrowing of cervical canal

Front 26

What happens to body temperature during the cycle and why does it happen?

Back 26

Progesterone acts on the hypothalamic thermo regulatory center. The basal body temperature increases during the luteal phase.

So a slight increase in temperature has indicated that the person has ovulated.

Front 27

What is the effect of progesterone on GnRH secretion? How does this occur?

Back 27

Progesterone decreases GnRH pulse frequency drastically. BUT this is NOT a negative feedback effect. This occurs through the activation of the hypothalamic opioid peptide system.

So GnRH/LH pulse frequency is LESS during LUTEAL phase.

Front 28

How long does the luteal phase? What happens at the end of it?

Back 28

The corpus luteum has a finite life span (14 +/- 2 days), after which menstruation occurs.

Front 29

What is menstruation, exactly?

Back 29

Menstruation marks the end of the cycle.

The decidual cells that are built up to provide a cushy environment for the egg are sluffed off. Superficial layers of the uterine mucosa become ischemic, cells lining endometrial glands are exfoliated, and there is necrosis of blood vessels.

Menstruation marks the end of the cycle.

The decidual cells that are built up to provide a cushy environment for the egg are sloughed off. Superficial layers of the uterine mucosa become ischemic, cells lining endometrial glands are exfoliated, and there is necrosis of blood vessels.

This results in 35-45 mL of NON-CLOTTING blood (fibrinolysin) for ~5 days.

Front 30

After menstruation, what initiates a new cycle? How does this initiating factor come about?

Back 30

Increase in FSH at the end of the luteal phase initiates a new cycle.

This increase occurs via:
1.) DECREASE IN GnRH PULSE FREQUENCY during luteal phase favors FSH synthesis, which accumulates in the pituitary gland.
2.) DECREASE IN ESTROGEN LEVELS results in decreased negative feedback on both LH and FSH.
3.) As corpus luteum disappears, there is a DECREASE IN INHIBIN A SECRETION, resulting in the removal of the slow negative feedback on FSH.

Front 31

A decrease in GnRH pulse frequency favors synthesis of ______ and disfavors synthesis of ________.

Back 31

FSH
LH

Front 32

What are the “fertile” and “sterile” periods for a woman during the cycle?

Back 32

Fertile: days of maximal estradiol levels in follicular phase.
Sterile: luteal phase

Front 33

How do hormonal contraceptives work?

Back 33

The ideal is to DESYNCHRONIZE natural hormone levels (as is what happens during actual pregnancy).

This ends up affecting:

1.) feedback signaling
2.) development of endometrium
3.) characteristics of cervical mucus
4.) myometrial tonicity
5.) transport of fertilized ovum