Physiology of Follicular Development

Question 1

During the development of the ovarian follicle, first meiotic arrest occurs at _________ and is associated with elevated levels of ________

Large antral follicles gain meiotic competence and stay in arrest until ____ surge (can stay in this stage 50 years!)

Answer 1

Prophase I; cAMP

LH

Question 2

Meiosis I finishes before ovulation, at which time the first ______ is extruded. The second is extruded after resumption of meiosis II only after fertilization

Answer 2

Polar body

Question 3

The second meiotic arrest during follicular development occurs during ________ and is associated with elevated levels of _________. If fertilization occurs, meiosis II resumes and there is rapid degradation of _____ as well as extrusion of a 2nd polar body

Answer 3

Metaphase II; MAPK proteins; MAPK

Question 4

The adult ovary can be divided into an inner medulla and outer cortex. Differentiate these two components

Answer 4

Inner medulla is highly vascular, contains nerves, interstitial cells, and lymphatics

Outer cortex consists of densely cellular stroma; ovarian follicles reside within the stroma at different points of their development

Question 5

3 phases of ovarian follicle cycle

Answer 5

Follicular phase
Ovulatory phase
Luteal phase

Question 6

During the follicular phase, the ______ ____ is the functional unit of the ovary

Answer 6

Ovarian follicle

Question 7

During the follicular phase, the ovarian follicle is the functional unit of the ovary; it performs ______ and _____ functions

Answer 7

Gametogenic; endocrine

[pre-menopausal cycling woman contains follicular structures at many different stages]

Question 8

The primordial follicle is surrounded by a single layer of _______ cells; it releases ______ factors but no steroid hormones at this stage. It represents the ovarian reserve, of which most will undergo ________

Answer 8

Pregranulosa; paracrine; atresia

Question 9

_______ follicles develop prior to the formation of the fluid-filled antral follicles

Answer 9

Pre-antral

Question 10

The primary follicle as it transitions to the preantral follicle consists of a central ______ oocyte, a single layer of granulosa cells which take on a _____ shape, the size of the follicle increases due to growth of the oocyte, and there is early production of secreted glycoproteins

Answer 10

Primary; cuboidal

Question 11

At what part of the follicular phase does the zona pellucida begin to develop?

Answer 11

Preantral follicle — early production of secreted glycoproteins ZP1, ZP2, and ZP3

Question 12

As the preantral follicle grows, it is associated with a secondary follicle, which consists of a primary oocyte surrounded by 3-6 layers of ______ ______ cells.

The secondary follicle secretes paracrine factors which induce local stromal cells to differentiate into ____ cells

Answer 12

Cuboidal granulosa

Thecal

Question 13

As the secondary follicle secretes paracrine factors to induce differentiation of stromal cells —> thecal cells, these can further be differentiated based on the inner glandular and highly vascular ________, and the fibrous capsule-like ______

Answer 13

Theca interna; theca externa

Question 14

Progression of the primary follicle to the secondary follicle requires increased vascularization — how does this occur?

Answer 14

The follicle migrates from the outer cortex to the inner cortex, closer to the ovarian vasculature

The follicles release angiogenic factors that induce development of 1-2 arterioles, generating a vascular wreath around the follicle

Question 15

The increased vascularization that occurs with progression to the secondary follicle also involves development of the _____ ____, which provides binding sites for sperm during fertilization

Answer 15

Zona pellucida

Question 16

The oocyte itself is avascular, but recieves its nutrition from ____ cells

Answer 16

Granulosa

Question 17

As preantral follicles grow and progress through secondary follicle stage, contact between the granulosa and oocyte is maintained. Cytoplasmic processes eventually penetrate the ZP and form ____ ____ at the oocyte surface, structures which also form between adjacent granulosa cells for intercellular communication

Answer 17

Gap junctions

Question 18

T/F: The preantral secondary follicle has minimal endocrine function

Answer 18

True

Question 19

The preantral secondary follicle has minimal endocrine function. Granulosa cells express ______ receptors (although growth at this point is not dependent on this hormone). Granulosa cells do not produce ovarian hormones at this point. Thecal cells are analogous to testicular Leydig cells. They express _____ receptors and their major product is ________, but at this point production is minimal or absent

Answer 19

FSH; LH; androstendione

Question 20

In the preantral to antral transition, proliferation of granulosa cells continues, leading to the continued increase in follicular size. _____ ______ from granulosa cell secretions begins to appear between.

Answer 20

Follicular fluid

Question 21

In the preantral to antral transition, proliferation of granulosa cells continues, leading to the continued increase in follicular size. Follicular fluid from granulosa cell secretions begins to appear between. Fluid drops eventually coalesce to form a singular _____ _____, marking the beginning of the _____ phase

Answer 21

Follicular antrum; antral

Question 22

The increase of follicular size that occurs with the beginning of the antral phase is dependent on what 3 factors?

Answer 22

Increase in antral size
Volume of follicular fluid
Proliferation of granulosa cells

Question 23

During the beginning of the antral phase, the oocyte becomes suspended in fluid surrounded by a dense mass of granulosa cells called the _____ ____

Answer 23

Cumulus oophorus

Question 24

The _____ phase is associated with a 100-fold increase in granulosa cells of 2 different populations: _____ and ______

Answer 24

Antral; mural; cumulus

Question 25

Differentiate the mural granulosa cells from the cumulus cells (cumulus oophorus/corona radiata) that can be differentiated during the antral phase

Answer 25

Mural granulosa = outer wall of follicle; become highly steroidogenic

Cumulus cells = maintain gap and adhesion junctions with oocyte. Released during ovulation with oocyte

Question 26

Growth during the antral phase becomes responsive to ________

Theca interna is responsive to ____

Granulosa cells are responsive to ____

Answer 26

Gonadotropins

LH

FSH

Question 27

What do the theca interna cells do in response to LH binding its receptors in the antral stage?

Answer 27

Synthesize androgens from acetate and cholesterol — androstenedione is major steroid product

Question 28

What do the granulosa cells do in response to FSH binding its receptors in the antral stage?

Answer 28

Convert androgens from thecal cells to estrogen via aromatization

Induces expression of LH receptors late in follicular phase

Question 29

The oocyte grows rapidly in the early stages of antral follicles, but growth slows in larger follicles. At the antral stage, the oocyte becomes competent to complete meiosis I at ovulation, but will maintain meiotic arrest until the midcycle ____ surge. Meiotic arrest is achieved by maintenance of elevated _____ levels in the mature oocyte

Answer 29

LH; cAMP

Question 30

Several large antral follicles are recruited to begin development each monthly cycle; there is selection of 1 dominant follicle early in the _____ phase, largely dependent on the follicles’ sensitivity to _____

Answer 30

Follicular; FSH

Question 31

Mural granulosa cells produce low levels of _____ and ________, causing decline in FSH levels. The largest follicle with the most FSH receptors becomes the dominant follicle, and the others will undergo _____, which is the apoptosis of oocytes and associated _____ cells

Answer 31

Estrogen; inhibin B; atresia; granulosa

Question 32

Midcycle, the dominant follicle becomes a large preovulatory follicle known as the _______ follicle

Answer 32

Graafian

Question 33

The _________ period is defined as the time from onset of LH surge to ovulation, only lasting about 32-36 hours. During this time structural changes are occuring in preparation of ovulation

There are also changes in steroidogenic function of the theca and mural granulosa cells; this prepares the cells for ________ process, formation of the ______, and increased production of _______

Answer 33

Periovulatory

Luteinization; corpus luteum; progesterone

Question 34

Follicular development can be induced as a treatment for sub- or infertility via Assisted Reproductive Procedures. What are 2 examples of this?

Answer 34

Clomiphene citrate

GnRH agonists or antagonists followed by FSH treatment

Question 35

Follicular development can be induced as a treatment for sub- or infertility via Assisted Reproductive Procedures. What is the MOA of clomiphene citrate?

Answer 35

Selective estrogen receptor modulator — inerferes with estrogen negative feedback leading to increased FSH availability

This increases antral follicle dev’t, multiple oocytes can be ovulated, and ovulation is triggered with LH or hCG to time process correctly

[this is the process of artificial insemination; 2-3 follicles will develop if successful]

Question 36

Follicular development can be induced as a treatment for sub- or infertility via Assisted Reproductive Procedures. What is the MOA of GnRH agonists or antagonists followed by FSH tx?

Answer 36

This prevents LH surge; extra FSH leads to development of multiple follicles. hCG trigger mimics LH surge to time egg collection

[this is the process of IVF; 15-16 follicles will develop if successful]

Question 37

The LH surge induces differentiation (luteinization) of granulosa to _____ _____ cells

Answer 37

Granulosa lutein

Question 38

At the time of LH surge, the thecal and mural granulosa cells express LH receptors. This induces a shift in steroidogenic activity. There is a transient inhibition of _____ expression, resulting in a rapid decline that reduces positive feedback on ____ secretion

Answer 38

Aromatase; LH

Question 39

Increased vascularization of granulosa during luteinization leads to increased cholesterol availability for _____ production

Answer 39

Progesterone

Question 40

The LH surge induces what structural changes in the follicle?

Answer 40

Release of cytokines and hydrolytic enzymes from theca and granulosa —> breakdown of follicle wall, tunica albuginea, surface epithelium

Cumulus-oocyte complex detaches (free floating in antrum)

Basal lamina of mural granulosa degraded — angiogenic factors released, increased blood supply to folicle/corpus luteum

LH surge induces oocte to progress to metaphase II

Question 41

During ovulation and luteinization, increased size of follicle and position in cortex causes a bulge on the ovarian surface. The bulging ____ wall becomes thin and avascular. CT breaks down and ruptures, causing follicular fluid, _____, and surrounding _______ cells to flow out to peritoneal cavity.

_____ then sweep the cumulus mass into oviductal ostium.

Answer 41

Stigma; oocyte; cumulus

Fimbria